immunoglobulin variable region

Summary

Summary: That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.

Top Publications

  1. pmc Two forms of loops generate the chromatin conformation of the immunoglobulin heavy-chain gene locus
    Changying Guo
    Gene Regulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224, USA
    Cell 147:332-43. 2011
  2. ncbi Phage antibodies: filamentous phage displaying antibody variable domains
    J McCafferty
    MRC Laboratory of Molecular Biology, Cambridge, UK
    Nature 348:552-4. 1990
  3. pmc IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis
    Xavier Brochet
    IMGT, the international ImMunoGeneTics information system, Laboratoire d ImmunoGenetique Moleculaire LIGM, Universite Montpellier 2, Institut de Genetique Humaine IGH, UPR CNRS 1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France
    Nucleic Acids Res 36:W503-8. 2008
  4. pmc Many chronic lymphocytic leukemia antibodies recognize apoptotic cells with exposed nonmuscle myosin heavy chain IIA: implications for patient outcome and cell of origin
    Charles C Chu
    The Feinstein Institute for Medical Research, North Shore Long Island Jewish LIJ Health System, Manhasset, NY 11030, USA
    Blood 115:3907-15. 2010
  5. pmc Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells
    U Klein
    Institute for Cancer Genetics, Departments of Pathology and Genetics and Development, Columbia University, New York, NY 10032, USA
    J Exp Med 194:1625-38. 2001
  6. ncbi By-passing immunization. Human antibodies from V-gene libraries displayed on phage
    J D Marks
    MRC Centre for Protein Engineering, Cambridge, U K
    J Mol Biol 222:581-97. 1991
  7. ncbi Making antibody fragments using phage display libraries
    T Clackson
    MRC Laboratory of Molecular Biology, Cambridge, UK
    Nature 352:624-8. 1991
  8. ncbi A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia
    George Adrian Calin
    Department of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA
    N Engl J Med 353:1793-801. 2005
  9. pmc Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120
    Chih Chin Huang
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 101:2706-11. 2004
  10. ncbi Reversible anergy of sIgM-mediated signaling in the two subsets of CLL defined by VH-gene mutational status
    C Ian Mockridge
    Molecular Immunology Group, Tenovus Laboratory, University of Southampton, Southampton General Hospital, Southampton, United Kingdom
    Blood 109:4424-31. 2007

Detail Information

Publications334 found, 100 shown here

  1. pmc Two forms of loops generate the chromatin conformation of the immunoglobulin heavy-chain gene locus
    Changying Guo
    Gene Regulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224, USA
    Cell 147:332-43. 2011
    ..Our observations provide a comprehensive view of the conformation of IgH alleles in pro-B cells and the mechanisms by which it is established...
  2. ncbi Phage antibodies: filamentous phage displaying antibody variable domains
    J McCafferty
    MRC Laboratory of Molecular Biology, Cambridge, UK
    Nature 348:552-4. 1990
    ..Here we show that complete antibody V domains can be displayed on the surface of fd bacteriophage, that the phage bind specifically to antigen and that rare phage (one in a million) can be isolated after affinity chromatography...
  3. pmc IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis
    Xavier Brochet
    IMGT, the international ImMunoGeneTics information system, Laboratoire d ImmunoGenetique Moleculaire LIGM, Universite Montpellier 2, Institut de Genetique Humaine IGH, UPR CNRS 1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France
    Nucleic Acids Res 36:W503-8. 2008
    ..The 'Advanced parameters' allow to modify default parameters used by IMGT/V-QUEST and IMGT/JunctionAnalysis according to the users' interest. IMGT/V-QUEST is freely available for academic research at http://imgt.cines.fr...
  4. pmc Many chronic lymphocytic leukemia antibodies recognize apoptotic cells with exposed nonmuscle myosin heavy chain IIA: implications for patient outcome and cell of origin
    Charles C Chu
    The Feinstein Institute for Medical Research, North Shore Long Island Jewish LIJ Health System, Manhasset, NY 11030, USA
    Blood 115:3907-15. 2010
    ..Taken together, our data indicate that a large proportion of CLL clones emerge from natural antibody-producing cells expressing immunoglobulins that recognize MEACs, and that this reactivity is associated with poor clinical outcome...
  5. pmc Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells
    U Klein
    Institute for Cancer Genetics, Departments of Pathology and Genetics and Development, Columbia University, New York, NY 10032, USA
    J Exp Med 194:1625-38. 2001
    ..Recent studies have shown that >50% of CLLs display hypermutated immunoglobulin variable region (IgV) sequences and a more favorable prognosis, suggesting that they may represent a distinct subset ..
  6. ncbi By-passing immunization. Human antibodies from V-gene libraries displayed on phage
    J D Marks
    MRC Centre for Protein Engineering, Cambridge, U K
    J Mol Biol 222:581-97. 1991
    ..Nevertheless, our results suggest that a single large phage display library can be used to isolate human antibodies against any antigen, by-passing both hybridoma technology and immunization...
  7. ncbi Making antibody fragments using phage display libraries
    T Clackson
    MRC Laboratory of Molecular Biology, Cambridge, UK
    Nature 352:624-8. 1991
    ..Phage display offers new ways of making antibodies from V-gene libraries, altering V-domain pairings and selecting for antibodies with good affinities...
  8. ncbi A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia
    George Adrian Calin
    Department of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA
    N Engl J Med 353:1793-801. 2005
    ..We investigated whether microRNA profiles are associated with known prognostic factors in CLL...
  9. pmc Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120
    Chih Chin Huang
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 101:2706-11. 2004
    ..When confronted by extraordinary viral defenses, the immune system unveils novel adaptive capabilities, with tyrosine sulfation enhancing the vocabulary of antigen recognition...
  10. ncbi Reversible anergy of sIgM-mediated signaling in the two subsets of CLL defined by VH-gene mutational status
    C Ian Mockridge
    Molecular Immunology Group, Tenovus Laboratory, University of Southampton, Southampton General Hospital, Southampton, United Kingdom
    Blood 109:4424-31. 2007
    ..Downstream signaling pathways, therefore, appear intact in CLL, locating anergy to sIgM, mainly in M-CLL. Integration of differential isotype-specific effects mediated by (auto)antigen may determine tumor behavior...
  11. ncbi Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides
    A Knappik
    MorphoSys AG, Lena Christ Str 48, Martinsried Munich, 82152, Germany
    J Mol Biol 296:57-86. 2000
    ..The small number of 49 master genes will allow future improvements to be incorporated quickly, and the separation of the frameworks may help in analyzing why nature has evolved these distinct subfamilies of antibody germline genes...
  12. pmc Protein engineering of antibody binding sites: recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in Escherichia coli
    J S Huston
    Creative BioMolecules, Hopkinton, MA 01748
    Proc Natl Acad Sci U S A 85:5879-83. 1988
    ..2 +/- 0.9) x 10(7) M-1] that was about a factor of 6 smaller than that found for 26-10 Fab fragments [Ka = (1.9 +/- 0.2) x 10(8) M-1] under the same buffer conditions, consisting of 0.01 M sodium acetate, pH 5.5/0.25 M urea...
  13. pmc CTCF-binding elements mediate control of V(D)J recombination
    Chunguang Guo
    Howard Hughes Medical Institute, The Children s Hospital, The Immune Disease Institute, Department of Genetics, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 477:424-30. 2011
    ..Our studies elucidate a long-sought Igh V(D)J recombination control region and indicate a new role for the generally expressed CTCF protein...
  14. pmc Visualization of looping involving the immunoglobulin heavy-chain locus in developing B cells
    Camil E Sayegh
    Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093, USA
    Genes Dev 19:322-7. 2005
    ..Based on these observations, we propose that Ig loci are repositioned by a looping mechanism prior to IgH V(D)J rearrangement to facilitate the joining of Ig variable, diversity, and joining segments...
  15. ncbi Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus
    M Odendahl
    Deutsches Rheuma ForschungsZentrum Berlin, Charite University Hospital, Berlin, Germany
    J Immunol 165:5970-9. 2000
    ..These results indicate that there are profound abnormalities in the various B cell compartments in SLE that respond differently to immunosuppressive therapy...
  16. ncbi Domain antibodies: proteins for therapy
    Lucy J Holt
    Domantis Limited, Granta Park, Abington, Cambridge CB1 6GS, UK
    Trends Biotechnol 21:484-90. 2003
    ..dAbs are bioactive as monomers and, owing to their small size and inherent stability, can be formatted into larger molecules to create drugs with prolonged serum half-lives or other pharmacological activities...
  17. ncbi Contribution of Vh gene replacement to the primary B cell repertoire
    Zhixin Zhang
    Division of Developmental and Clinical Immunology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Immunity 19:21-31. 2003
    ..Surprisingly, the residual 3' sequences of replaced V(H) genes contribute charged amino acids to the CDR3 region, a hallmark of autoreactive antibodies...
  18. ncbi Bovine IgG repertoire is dominated by a single diversified VH gene family
    M C Sinclair
    Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland
    J Immunol 159:3883-9. 1997
    ..Comparison of germline VH sequences with those gathered from adult bovine splenic cDNA demonstrates a pattern of nucleotide substitution that is consistent with diversification through somatic hypermutation...
  19. doi BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgV H unmutated chronic lymphocytic leukemia (CLL) cells
    Anna Guarini
    Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy
    Blood 112:782-92. 2008
    ....
  20. ncbi Frequent occurrence of identical heavy and light chain Ig rearrangements
    K J Seidl
    Department of Genetics, Beckman Center B007, Stanford University School of Medicine, CA 94305 5125, USA
    Int Immunol 9:689-702. 1997
    ..As suggested by initial studies of dominant idiotype expression, these findings confirm that clonal expansion is only one of the mechanisms contributing to the establishment of recurrent rearrangements...
  21. ncbi Somatic insertions and deletions shape the human antibody repertoire
    R M de Wildt
    MRC Centre for Protein Engineering and MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK
    J Mol Biol 294:701-10. 1999
    ....
  22. pmc Regulation of inherently autoreactive VH4-34 B cells in the maintenance of human B cell tolerance
    A E Pugh-Bernard
    Department of Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Clin Invest 108:1061-70. 2001
    ....
  23. ncbi Lack of N regions in antigen receptor variable region genes of TdT-deficient lymphocytes
    T Komori
    Howard Hughes Medical Institute, Children s Hospital, Boston, MA 02115
    Science 261:1171-5. 1993
    ....
  24. ncbi Somatic hyperconversion diversifies the single Vh gene of the chicken with a high incidence in the D region
    C A Reynaud
    Basel Institute for Immunology, Switzerland
    Cell 59:171-83. 1989
    ..Allelic exclusion appears to be performed by restriction of a complete VDJ rearrangement to a single allele...
  25. pmc Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains
    S L Morrison
    Proc Natl Acad Sci U S A 81:6851-5. 1984
    ..The transformed cell lines remained tumorigenic in mice and the chimeric molecules were present in the ascitic fluids and sera of tumor-bearing mice...
  26. pmc Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions
    Robert W Maul
    Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA
    Nat Immunol 12:70-6. 2011
    ..Our data provide direct evidence for the model that AID functions by deaminating cytosine residues in DNA...
  27. pmc GANP-mediated recruitment of activation-induced cytidine deaminase to cell nuclei and to immunoglobulin variable region DNA
    Kazuhiko Maeda
    Department of Immunology, Graduate School of Life Sciences, Kumamoto University, 1 1 1 Honjo, Kumamoto 860 8556, Japan
    J Biol Chem 285:23945-53. 2010
    ..These data suggest that GANP may serve as an essential link required to transport AID to B-cell nuclei and to target AID to actively transcribed IgV regions...
  28. ncbi Assembly of a functional immunoglobulin Fv fragment in Escherichia coli
    A Skerra
    Genzentrum der Universität München, Max Planck Institut fur Biochemie, Martinsried, FRG
    Science 240:1038-41. 1988
    ..This expression system should facilitate future protein engineering experiments on antibodies...
  29. doi Dichotomy in NF-kappaB signaling and chemoresistance in immunoglobulin variable heavy-chain-mutated versus unmutated CLL cells upon CD40/TLR9 triggering
    J M Tromp
    Department of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Oncogene 29:5071-82. 2010
    ..Thus, a distinction in NF-kappaB activation and drug susceptibility in mutated versus unmutated (LN-like) CLL cells was uncovered, which was causally linked to Bcl-X(L) levels...
  30. pmc Localized epigenetic changes induced by DH recombination restricts recombinase to DJH junctions
    Ramesh Subrahmanyam
    Laboratory of Molecular Biology and Immunology, National Institute on Aging, US National Institutes of Health, Baltimore, Maryland, USA
    Nat Immunol 13:1205-12. 2012
    ..We propose that V(H) recombination is precise, because these changes did not extend to germline D(H) segments located 5' of the DJ(H) junction...
  31. ncbi Generation of high-affinity antibody against T cell-dependent antigen in the Ganp gene-transgenic mouse
    Nobuo Sakaguchi
    Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto, Japan
    J Immunol 174:4485-94. 2005
    ..90 x 10(-11) M) with neutralizing activity. These results demonstrated that GANP is involved in V region alteration generating high-affinity Ab...
  32. ncbi Metal binding properties of a monoclonal antibody directed toward metal-chelate complexes
    D A Blake
    Department of Ophthalmology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA
    J Biol Chem 271:27677-85. 1996
    ..The key residue for cadmium binding in the model for 2A81G5 appeared to be histidine 96 in the heavy chain...
  33. ncbi Detailed analysis of the E2-IgM complex in hepatitis C-related type II mixed cryoglobulinaemia
    S Ferri
    Venetian Institute of Molecular Medicine VIMM, Padova, Italy
    J Viral Hepat 13:166-76. 2006
    ....
  34. doi Evidence for the significant role of immunoglobulin light chains in antigen recognition and selection in chronic lymphocytic leukemia
    Anastasia Hadzidimitriou
    Institute of Agrobiotechnology, Centre for Research and Technology, Thessaloniki, Greece
    Blood 113:403-11. 2009
    ..Therefore, CLL is characterized not only by stereotyped HCDR3 and heavy chains but, rather, by stereotyped BCRs involving both chains, which generate distinctive antigen-binding grooves...
  35. pmc Content and organization of the human Ig VH locus: definition of three new VH families and linkage to the Ig CH locus
    J E Berman
    Howard Hughes Medical Institute, College of Physicians and Surgeons of Columbia University, New York, NY 10032
    EMBO J 7:727-38. 1988
    ..Finally, we provide the first report of the physical linkage of the variable and constant loci of a human Ig gene family by demonstrating that the most proximal known human VH segments lie within 100 kb of the constant region locus...
  36. doi The immunoglobulin heavy chain locus in the platypus (Ornithorhynchus anatinus)
    F Gambón-Deza
    Vigo University Hospital Complex, Pontevedra, Spain
    Mol Immunol 46:2515-23. 2009
    ..These results suggest that a fast VH turnover took place in platypus and this gave rise to a family with a high VH gene number and the disappearance of the earlier VH families...
  37. ncbi Biophysical properties of human antibody variable domains
    Stefan Ewert
    Biochemisches Institut, Universitat Zurich, Winterthurerstr 190, CH 8057 Zurich, Switzerland
    J Mol Biol 325:531-53. 2003
    ..On the basis of these analyses and model structures, we suggest possibilities for further improvement of the biophysical properties of individual frameworks and give recommendations for library design...
  38. ncbi Reliable and controllable antibody fragment selections from Camelid non-immune libraries for target validation
    Peter Verheesen
    University of Utrecht, Department of Molecular and Cellular Biology, Utrecht, The Netherlands
    Biochim Biophys Acta 1764:1307-19. 2006
    ....
  39. pmc VBASE2, an integrative V gene database
    Ida Retter
    Department of Experimental Immunology, German Research Centre for Biotechnology, Mascheroder Weg 1, D 38124 Braunschweig, Germany
    Nucleic Acids Res 33:D671-4. 2005
    ..VBASE2 can be accessed either by a web-based text query or by a sequence similarity search with the DNAPLOT software. VBASE2 is available at http://www.vbase2.org, and the DAS server is located at http://www.dnaplot.com/das...
  40. pmc bcl-2 transgene expression inhibits apoptosis in the germinal center and reveals differences in the selection of memory B cells and bone marrow antibody-forming cells
    K G Smith
    The Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Victoria 3050, Australia
    J Exp Med 191:475-84. 2000
    ..Continuous competition for antigen does, however, explain formation of the memory compartment...
  41. pmc Effects of intracellular expression of anti-huntingtin antibodies of various specificities on mutant huntingtin aggregation and toxicity
    Ali Khoshnan
    Biology Division, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 99:1002-7. 2002
    ..Therefore, these anti-htt scFvs can be used to investigate the role of the polyP and polyQ domains in HD pathogenesis, and antibody binding to the polyP domain has potential therapeutic value in HD...
  42. ncbi ERIC recommendations on IGHV gene mutational status analysis in chronic lymphocytic leukemia
    P Ghia
    Leukemia 21:1-3. 2007
  43. ncbi Tolerogenic treatment of lupus mice with consensus peptide induces Foxp3-expressing, apoptosis-resistant, TGFbeta-secreting CD8+ T cell suppressors
    Bevra H Hahn
    Department of Medicine, Division of Rheumatology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    J Immunol 175:7728-37. 2005
    ....
  44. ncbi A critical role of lambda 5 protein in B cell development
    D Kitamura
    Institute for Genetics, University of Cologne, Germany
    Cell 69:823-31. 1992
    ..However, the blockade is leaky, allowing B cells to populate the peripheral immune system at a low rate. These cells are allelically excluded and able to respond to antigen...
  45. doi Nanobodies®: new ammunition to battle viruses
    Peter Vanlandschoot
    Ablynx NV, Ghent, Belgium
    Antiviral Res 92:389-407. 2011
    ..The straightforward formatting into bivalent, multivalent, and/or multispecific Nanobodies allowed tailoring molecules for potency and cross-reactivity against viral targets with high sequence diversity...
  46. ncbi Expressed swine VH genes belong to a small VH gene family homologous to human VHIII
    J Sun
    Department of Microbiology, College of Medicine, University of Iowa, Iowa City 52242
    J Immunol 153:5618-27. 1994
    ..Analyses of individual genomic bands by single strand conformational polymorphism and sequence analysis suggest that the number of VHIII-related genes in the swine genome is < 20...
  47. ncbi Editors and editing of anti-DNA receptors
    H Li
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
    Immunity 15:947-57. 2001
    ..Among the edited B cells is a subset of multispecific cells that express multiple receptors. One consequence of multispecificity is partial autoreactivity; these multispecific B cells may contribute to autoimmunity...
  48. ncbi Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors
    David G Oscier
    Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom
    Blood 100:1177-84. 2002
    ..These data should facilitate the design of new trials for the management of patients presenting with advanced disease or poor prognosis early stage disease...
  49. doi Structural repertoire of immunoglobulin λ light chains
    Anna Chailyan
    Department of Biochemical Sciences, Sapienza University of Rome, p le A Moro, 5 00185 Rome I, Italy
    Proteins 79:1513-24. 2011
    ....
  50. pmc Frequent occurrence of deletions and duplications during somatic hypermutation: implications for oncogene translocations and heavy chain disease
    T Goossens
    Institute for Genetics, University of Cologne, 50931 Cologne, Germany
    Proc Natl Acad Sci U S A 95:2463-8. 1998
    ....
  51. ncbi Polyreactivity of antibody molecules
    Abner Louis Notkins
    Experimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research NIH, Bethesda, MD 20892 4322, USA
    Trends Immunol 25:174-9. 2004
  52. ncbi ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile
    Adrian Wiestner
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
    Blood 101:4944-51. 2003
    ..We developed reverse transcriptase-polymerase chain reaction and immunohistochemical assays for ZAP-70 expression that can be applied clinically and would yield important prognostic information for patients with CLL...
  53. ncbi Flow-cytometric isolation of human antibodies from a nonimmune Saccharomyces cerevisiae surface display library
    Michael J Feldhaus
    Pacific Northwest National Laboratories, Biological Sciences Division, 902 Battelle Blvd, P O Box 999, Richland, WA 99352, USA
    Nat Biotechnol 21:163-70. 2003
    ..The ability to use multiplex library screening demonstrates the usefulness of this approach for high-throughput antibody isolation for proteomics applications...
  54. ncbi Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus
    David Jung
    Howard Hughes Medical Institute, Children s Hospital, CBR Institute for Biomedical Research, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Immunol 24:541-70. 2006
    ..In this review, we summarize advances that have been made in understanding how V(D)J recombination at the IgH locus is controlled and discuss important areas for future investigation...
  55. pmc Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia
    Bradley T Messmer
    North Shore LIJ Research Institute, 350 Community Dr, Manhasset, NY 11030, USA
    J Exp Med 200:519-25. 2004
    ..These shared, stereotyped Ig molecules may be valuable probes for antigen identification and important targets for cross-reactive idiotypic therapy...
  56. ncbi Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool
    A Honegger
    Biochemisches Institut der Universitat Zurich, Winterthurerstrasse 190, Zurich, CH 8057, Switzerland
    J Mol Biol 309:657-70. 2001
    ..A number of methods are presented that allow the automated projection of information derived from individual structures or from the comparison of multi-structure alignments onto a graphical representation of the sequence alignment...
  57. pmc 129-derived strains of mice are deficient in DNA polymerase iota and have normal immunoglobulin hypermutation
    John P McDonald
    Laboratory of Genomic Integrity, Building 6, Room 1A13, NICHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 2725, USA
    J Exp Med 198:635-43. 2003
    ..Thus, either poliota does not participate in hypermutation, or its role is nonessential and can be readily assumed by another low-fidelity polymerase...
  58. ncbi Differential signaling via surface IgM is associated with VH gene mutational status and CD38 expression in chronic lymphocytic leukemia
    Stuart Lanham
    Molecular Immunology Group, Tenovus Research Laboratory, Southampton University Hospitals Trust, Southampton, United Kingdom
    Blood 101:1087-93. 2003
    ..The prognostic power of the in vitro response to IgM ligation remains to be determined in a large series, but the simple technology involved may present an alternative or additional test for predicting clinical course...
  59. ncbi Aggregation-resistant domain antibodies selected on phage by heat denaturation
    Laurent Jespers
    Nat Biotechnol 22:1161-5. 2004
    ..The method should be useful for making aggregation-resistant proteins and for helping to identify features that promote or prevent protein aggregation, including those responsible for misfolding diseases...
  60. pmc Immunoglobulin gene mutations and frequent use of VH1-69 and VH4-34 segments in hepatitis C virus-positive and hepatitis C virus-negative nodal marginal zone B-cell lymphoma
    R Marasca
    Department of Medical Sciences, Section of Hematology, University of Modena and Reggio Emilia, Modena, Italy
    Am J Pathol 159:253-61. 2001
    ....
  61. pmc B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5
    Kristen Johnson
    Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Nat Immunol 5:853-61. 2004
    ....
  62. pmc The antigen-binding domain of a human IgG-anti-F(ab')2 autoantibody
    M Welschof
    Institute of Immunology, Department of Transplantation Immunology, University of Heidelberg, Germany
    Proc Natl Acad Sci U S A 94:1902-7. 1997
    ....
  63. ncbi Generating improved single-chain Fv molecules for tumor targeting
    G P Adams
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    J Immunol Methods 231:249-60. 1999
    ..In this review, we describe a number of these methods and discuss some of the characteristics that may belong to an optimal antibody-based targeting vehicle...
  64. ncbi A helper phage to improve single-chain antibody presentation in phage display
    S Rondot
    Molekulargenetisches Labor Prof. Raue, Friedrich-Ebert-Anlage 28, 69117 Heidelberg, Germany
    Nat Biotechnol 19:75-8. 2001
    ..Thus, hyperphage is particularly useful in stoichiometric situations, when there is little chance that a single phage will locate the desired antigen...
  65. ncbi A new recombinant single chain trispecific antibody recruits T lymphocytes to kill CEA (carcinoma embryonic antigen) positive tumor cells in vitro efficiently
    Xiang Bin Wang
    The Institute of Genetics and Developmental Biology, Chinese Academy of Science, 100101, Beijing, China
    J Biochem 135:555-65. 2004
    ....
  66. ncbi Dimeric and trimeric antibodies: high avidity scFvs for cancer targeting
    A A Kortt
    CSIRO Health Science and Nutrition, 343 Royal Parade, VIC 3052, Parkville, Australia
    Biomol Eng 18:95-108. 2001
    ..The more challenging trispecific multimers (triabodies) remain to be described...
  67. ncbi Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: Pathogenetic implications and clinical correlations
    Kostas Stamatopoulos
    Hematology Department and HCT Unit, G Papanicolaou Hospital, Thessaloniki, Greece
    Blood 109:259-70. 2007
    ..These findings suggest that a particular antigen-binding site can be critical in determining the clinical features and outcome for at least some CLL patients...
  68. ncbi VH gene usage in immunoglobulin E responses of seasonal rhinitis patients allergic to grass pollen is oligoclonal and antigen driven
    J M Davies
    Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Commercial Road, Melbourne, VIC 3004, Australia
    Clin Exp Allergy 34:429-36. 2004
    ....
  69. doi Disulfide bond introduction for general stabilization of immunoglobulin heavy-chain variable domains
    Dirk Saerens
    Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Pleinlaan 2, B 1050 Brussels, Belgium
    J Mol Biol 377:478-88. 2008
    ..Interestingly, only the extra naturally occurring cystine consistently increased the conformational and thermal stabilities of wild-type Nanobodies without affecting antigen binding...
  70. pmc No evidence for the use of DIR, D-D fusions, chromosome 15 open reading frames or VH replacement in the peripheral repertoire was found on application of an improved algorithm, JointML, to 6329 human immunoglobulin H rearrangements
    Line Ohm-Laursen
    Department of Clinical Immunology, Odense University Hospital, Odense, Denmark
    Immunology 119:265-77. 2006
    ..An online version 1.0 of JointML is available at http://www.cbs.dtu.dk/services/VDJsolver...
  71. pmc A multifunctional element in the mouse Igκ locus that specifies repertoire and Ig loci subnuclear location
    Yougui Xiang
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    J Immunol 186:5356-66. 2011
    ..Hence, Sis is a novel multifunctional element that specifies repertoire and heterochromatin localization to Ig genes...
  72. ncbi DNA polymerase eta contributes to strand bias of mutations of A versus T in immunoglobulin genes
    Vladimir I Mayorov
    Department of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA 31207, USA
    J Immunol 174:7781-6. 2005
    ..Because polymerase eta inserts more mutations opposite template T than template A, it would generate more substitutions of A on the newly synthesized strand...
  73. ncbi The human antibody repertoire specific for rabies virus glycoprotein as selected from immune libraries
    R Arjen Kramer
    Crucell Holland B V, Leiden, The Netherlands
    Eur J Immunol 35:2131-45. 2005
    ..The obtained specificities expand the set of human anti-RV antibodies eligible for inclusion in an antibody cocktail aimed for use in rabies post-exposure prophylaxis...
  74. pmc Positive selection of the peripheral B cell repertoire in gut-associated lymphoid tissues
    Ki Jong Rhee
    Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
    J Exp Med 201:55-62. 2005
    ..We propose that interaction of such a superantigen with V(H)a B cells results in their selective expansion...
  75. ncbi Increased affinity leads to improved selective tumor delivery of single-chain Fv antibodies
    G P Adams
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Cancer Res 58:485-90. 1998
    ..These results indicate that affinity can significantly impact the in vivo tumor-specific retention of scFv molecules...
  76. ncbi Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sjögren's syndrome
    Arne Hansen
    University Hospital Charite, Berlin, Germany
    Arthritis Rheum 46:2160-71. 2002
    ..To delineate the mechanism of the abnormalities in B cell biology found in patients with primary Sjögren's syndrome (SS)...
  77. ncbi A definitive set of oligonucleotide primers for amplifying human V regions
    D Sblattero
    International School for Advanced Studies, Trieste, Italy
    Immunotechnology 3:271-8. 1998
    ..All functional germline V genes have recently been catalogued in a database, V BASE [1]. Previously published primer sets are unable to recognise all these V genes...
  78. pmc Efficient construction of a large nonimmune phage antibody library: the production of high-affinity human single-chain antibodies to protein antigens
    M D Sheets
    Department of Molecular Cell Biology, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 95:6157-62. 1998
    ..Such libraries should prove especially useful for generating reagents to study the function of gene products identified by genome projects...
  79. ncbi Analysis of IgE antibodies from a patient with atopic dermatitis: biased V gene usage and evidence for polyreactive IgE heavy chain complementarity-determining region 3
    Michael R Edwards
    School of Microbiology and Immunology, University of New South Wales, Kensington, Australia
    J Immunol 168:6305-13. 2002
    ..These results suggest that some IgE Abs may bind more than one Ag, which would have important implications for understanding the multiple sensitivities seen in conditions such as atopic dermatitis...
  80. pmc "Diabodies": small bivalent and bispecific antibody fragments
    P Holliger
    Medical Research Council Centre for Protein Engineering, Cambridge, United Kingdom
    Proc Natl Acad Sci U S A 90:6444-8. 1993
    ..Diabodies offer a ready means of constructing small bivalent and bispecific antibody fragments in bacteria...
  81. pmc Low-level hypermutation in T cell-independent germinal centers compared with high mutation rates associated with T cell-dependent germinal centers
    Kai Michael Toellner
    Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham B15 2TT, United Kingdom
    J Exp Med 195:383-9. 2002
    ..It is concluded that efficient activation of hypermutation depends on interaction with T cells, but some hypermutation may be induced without such signals, even outside germinal centers...
  82. doi IgTree: creating Immunoglobulin variable region gene lineage trees
    Michal Barak
    The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan 52900, Israel
    J Immunol Methods 338:67-74. 2008
    ..Our aim was to create and implement an algorithm that can generate lineage trees from immunoglobulin variable region gene sequences. The IgTree program implements the algorithm we developed, and generates lineage trees...
  83. ncbi Reliable cloning of functional antibody variable domains from hybridomas and spleen cell repertoires employing a reengineered phage display system
    A Krebber
    Biochemisches Institut der Universitat Zurich, Switzerland
    J Immunol Methods 201:35-55. 1997
    ..To maximize soluble expression of functional scFvs subsequent to cloning, a compatible vector series to simplify modification, detection, multimerization and rapid purification of recombinant antibody fragments was constructed...
  84. pmc Identification of core DNA elements that target somatic hypermutation
    Kristin M Kohler
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    J Immunol 189:5314-26. 2012
    ..We propose that multiple, dispersed DNA elements collaborate to recruit and activate the mutational machinery at Ig gene variable regions during SHM...
  85. ncbi A CD33-specific single-chain immunotoxin mediates potent apoptosis of cultured human myeloid leukaemia cells
    Michael Schwemmlein
    University of Erlangen Nuremberg, Erwin Rommel Strasse 3, D 91058 Erlangen, Germany
    Br J Haematol 133:141-51. 2006
    ..The pronounced antigen-restricted cytotoxicity of the novel fusion protein makes it a candidate for further evaluation of its therapeutic potential...
  86. ncbi Clonal instability of V region hypermutation in the Ramos Burkitt's lymphoma cell line
    W Zhang
    Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Int Immunol 13:1175-84. 2001
    ..These results suggest that the hypermutation phenotype is inherently unstable in Ramos and that long culture periods favor outgrowth of non-mutating cells that express lower levels of AID...
  87. doi Molecular mechanism of immunoglobulin V-region diversification regulated by transcription and RNA metabolism in antigen-driven B cells
    N Sakaguchi
    Department of Immunology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
    Scand J Immunol 73:520-6. 2011
    ..GANP augments the access of AID towards IgV-regions in B cells. Here, we review the role of GANP in acquired immunity through the detailed analysis of the molecular mechanism generating SHM specifically at IgV-regions in B cells...
  88. pmc Skewed primary Igκ repertoire and V-J joining in C57BL/6 mice: implications for recombination accessibility and receptor editing
    Miyo Aoki-Ota
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 188:2305-15. 2012
    ..Usage patterns were remarkably stable in different selective conditions. Overall, the primary κ repertoire is highly skewed by preferred rearrangements, limiting Ab diversity, but potentially facilitating receptor editing...
  89. ncbi Immunoglobulin diversification in B cell malignancies: internal splicing of heavy chain variable region as a by-product of somatic hypermutation
    R J Bende
    Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
    Leukemia 16:636-44. 2002
    ..The significance of alternative IgV(H) processing in B cell malignancies and as a potential mechanism of somatic Ig diversification is discussed...
  90. ncbi Humoral immune responses in Cr2-/- mice: enhanced affinity maturation but impaired antibody persistence
    Z Chen
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Immunol 164:4522-32. 2000
    ..These observations suggest that B cell activation/survival signals mediated by CD21 and/or the retention of Ag by CD21/CD35 play important roles in the generation, quality, and maintenance of serum Ab...
  91. ncbi Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development
    Steven T Kosak
    Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA
    Science 296:158-62. 2002
    ..We suggest that subnuclear positioning represents a novel means of regulating transcription and recombination of IgH and Igkappa loci during lymphocyte development...
  92. pmc Isolation of llama antibody fragments for prevention of dandruff by phage display in shampoo
    Edward Dolk
    Department of Molecular and Cellular Biology, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands
    Appl Environ Microbiol 71:442-50. 2005
    ..The combination of the unique properties of VHHs together with applied phage display and protein engineering is a powerful method for obtaining highly stable VHHs that can be used in a wide range of applications...
  93. doi PIGS: automatic prediction of antibody structures
    Paolo Marcatili
    Department of Biochemical Sciences and Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University, P le A Moro 5, 00185 Rome, Italy
    Bioinformatics 24:1953-4. 2008
    ..It allows the user to select the templates for the frameworks and the loops using different strategies. The final output is a full-fledged 3D model of the variable domains of the target immunoglobulin...
  94. pmc Transcription of productive and nonproductive VDJ-recombined alleles after IgH allelic exclusion
    Janssen Daly
    Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK
    EMBO J 26:4273-82. 2007
    ..Thus, after the establishment of IgH allelic exclusion, monoallelic recruitment to heterochromatin does not silence VDJ- or DJ-transcription, but serves another purpose...
  95. ncbi Novel anti-CD30 recombinant immunotoxins containing disulfide-stabilized Fv fragments
    Satoshi Nagata
    Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4264, USA
    Clin Cancer Res 8:2345-55. 2002
    ....
  96. pmc Preferential use of the VH5-51 gene segment by the human immune response to code for antibodies against the V3 domain of HIV-1
    Miroslaw K Gorny
    Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
    Mol Immunol 46:917-26. 2009
    ..The preferential usage of selected Ig gene segments and the characteristic pattern of Ig gene usage by anti-V3 mAbs can be related to the conserved structure of the V3 region...
  97. pmc Cutting edge: developmental stage-specific recruitment of cohesin to CTCF sites throughout immunoglobulin loci during B lymphocyte development
    Stephanie C Degner
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 182:44-8. 2009
    ..The differential binding of cohesin to CTCF sites may promote multiple loop formation and thus effective V(D)J recombination...
  98. ncbi Humanization of a chicken anti-IL-12 monoclonal antibody
    Naoya Tsurushita
    Protein Design Labs, Inc, 34801 Campus Drive, Fremont, CA 94555, USA
    J Immunol Methods 295:9-19. 2004
    ....
  99. pmc The role of antigen in the selection of the human V3-23 immunoglobulin heavy chain variable region gene
    C G Mackworth-Young
    Kennedy Institute of Rheumatology, London, UK
    Clin Exp Immunol 134:420-5. 2003
    The immune system mounts antibody responses using few of the available immunoglobulin variable region (IgV) genes with some, such as the V3-23 heavy chain gene, regularly over-represented in responses to many antigens...
  100. pmc A flow cytometry-based strategy to identify and express IgM from VH1-69+ clonal peripheral B cells
    Edgar D Charles
    Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA
    J Immunol Methods 363:210-20. 2011
    ..We anticipate that this system will be useful for the cloning and expression of mAbs partially encoded by VH1-69 and for determination of the reactivity patterns of polyspecific, low-affinity IgMs of human pathogenic importance...
  101. pmc FAS is highly expressed in the germinal center but is not required for regulation of the B-cell response to antigen
    K G Smith
    Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia
    Proc Natl Acad Sci U S A 92:11628-32. 1995
    ..The results suggest that the size and composition of B-cell compartments in the humoral immune response are regulated by mechanisms that do not require FAS...

Research Grants66

  1. Development of transformed lactobacilli as a microbicide
    Richard B Markham; Fiscal Year: 2010
    ....
  2. Long-Range Genetic and Epigenetic Control of Igh Gene Assembly
    Eugene M Oltz; Fiscal Year: 2010
    ..We propose studies to address how precursor B cells control long-range changes in the spatial organization of the immunoglobulin heavy chain locus to ensure its proper assembly and pursuant generation of an adaptive immune system. ..
  3. ACTIVATION INDUCED DEAMINASE (AID) INTERACTING PROTEINS
    Michel C Nussenzweig; Fiscal Year: 2011
    ..Epub ahead of print] ..
  4. Brain tumors with regulatory T-cells treated with EGFRvIII-specific T-cells
    John H Sampson; Fiscal Year: 2013
    ....
  5. Accessibility Control of Antigen Receptor Gene Assembly
    Eugene M Oltz; Fiscal Year: 2013
    ..We propose studies to address how precursor T lymphocytes activate the T cell receptor beta locus at the earliest stages of thymocyte development to ensure its proper assembly by V(D)J recombination. ..
  6. Humanization of a mouse anti-OX40 monoclonal antibody to treat cancer
    Andrew D Weinberg; Fiscal Year: 2012
    ..Agonox is proposing to genetically engineer the mouse antibody to become more "human" so that several rounds of treatment may be administered in order to achieve an even better outcome for cancer patients in future clinical trials. ..
  7. Validating a novel biomarker of clinical progression and survival in CLL
    Randall S Davis; Fiscal Year: 2013
    ....
  8. EVOLUTIONARY ORIGINS OF IMMUNE-TYPE GENES
    GARY WILLIAM LITMAN; Fiscal Year: 2013
    ..provide the first line of defense, are 10-fold increased in number than are seen in mammals and 2) an immunoglobulin variable region-containing immune-type receptor exhibits regionalized hypervariation that is associated with unique ..
  9. HIV-driven B cell activation: role in the genesis of AIDS-related lymphoma
    Otoniel Martinez-Maza; Fiscal Year: 2013
    ....
  10. MECHANISM OF IMMUNOGLOBULIN HYPERMUTATION
    URSULA B STORB; Fiscal Year: 2012
    ..Most of the experiments will at first be carried out in B cell lines in culture that undergo somatic hypermutation. If conclusive in cultured cells, some experiments will be checked in normal and transgenic mice. ..
  11. Regulation of antibody diversification and production in HIV-1 infection
    Andrea Cerutti; Fiscal Year: 2012
    ..The goal of this application is to elucidate the mechanisms by which HIV-1 causes B cell dysfunctions. Ultimately, findings deriving from the proposed studies should help develop more effective vaccines against HIV-1. ..
  12. Role of the BCR in B Cell Chronic Lymphocytic Leukemia
    Diane F Jelinek; Fiscal Year: 2013
    ..Through these studies, we aim to add novel insight into the etiology of this disease and are optimistic that this information can be used to devise timely novel therapeutic interventions. ..
  13. Mucosal Adjuvants Targeting Dendritic Cells
    John G Nedrud; Fiscal Year: 2010
    ..It will develop a new class of intranasal vaccines which combine antigens, a substance to enhance immune responses (an adjuvant) and a way to direct the vaccine to the tissues where an immune response to the vaccine is initiated. ..
  14. Role of autoantibody isotype in pemphigus pathogenesis
    Aimee S Payne; Fiscal Year: 2013
    ..As similar isotype profiles occur in pemphigoid, epidermolysis bullosa acquisita, and other chronic autoimmune conditions, our studies may have therapeutic relevance for a broad range of autoantibody-mediated diseases. ..
  15. Proteolytic Regulation of Troponin T &Cardiac Function
    Jian Ping Jin; Fiscal Year: 2013
    ..Using integrated experimental systems, this study will gain new knowledge for the structure-function relationships of TnT and lay a foundation for future development of new treatment of ischemic heart disease and heart failure. ..
  16. A novel glycosylation-associated protein is required for fimbriae biogenesis
    Haley L Echlin; Fiscal Year: 2013
    ..To test this hypothesis, I propose to investigate these specific aims: 1) assess the biochemical function of Gap2;2) analyze Gap2 interaction with other proteins in the Fap1 cluster;3) determine the role Gap2 plays in Fap1 biogenesis. ..
  17. ANTIBODY V GENE EXPRESSION B CELL LYMPHOCYTIC LEUKEMIA
    Thomas J Kipps; Fiscal Year: 2013
    ..Further studies could enable us to refine this approach toward development of truly effective immune therapy for patients with this disease. ..
  18. Phage Display Investigations of TDP-43
    RAYMOND PHILIP contact ROOS; Fiscal Year: 2010
    ..Together, this work may provide insight into why mutations of this protein cause ALS, and potentially provide a direction for treatment of sporadic and inherited ALS (as well as other neurodegenerative diseases). ..
  19. Interaction of AIDS-associated microbes with radiation
    Ekaterina Dadachova; Fiscal Year: 2010
    ..Understanding of immune mechanisms involved in the RIT outcomes will help to devise clinical protocols with expanded therapeutic window for treatment of patients in different stages of the disease. ..
  20. Control of B cell Development by YY1
    Michael L Atchison; Fiscal Year: 2013
    ..Understanding these functions of YY1 may provide multiple avenues for possible therapeutic intervention in diseases caused by PcG dysfunction, or aberrant stem cell self renewal. ..
  21. Molecular Principles of TCR Recognition and Activation by Peptide MHC
    KENAN CHRISTOPHER GARCIA; Fiscal Year: 2011
    ..abstract_text> ..
  22. MPER broadly neutralizing antibody knockin mice to study anti-HIV Bcell responses
    Laurent K Verkoczy; Fiscal Year: 2013
    ..These experiments should be helpful in formulating novel strategies for properly eliciting protective HIV-1 antibodies in patients. ..
  23. Infectious origins of childhood leukemia
    MARKUS MUSCHEN; Fiscal Year: 2013
    ..g. TEL-AML1) pre-B cell clone to acquire critical secondary lesions. ..
  24. Passive Immunotherapy for Pediatric Mutans Streptococcal Infections
    Martin Taubman; Fiscal Year: 2009
    ..abstract_text> ..
  25. CELLULAR AND STRUCTURAL STUDIES OF MYELOMA MUTANTS
    BARBARA BIRSHTEIN; Fiscal Year: 2009
    ..Only two major cis regulatory elements are known, i.e. the intronic enhance r and a complex w'regulatory region containing four known enhancers-a major target. ..
  26. Inhibition of heteromeric erbB kinases
    Mark I Greene; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: We are developing new classes of antibody therapeutics to treat breast cancers that have become resistant to therapeutics such as Herceptin or tyrosine kinase inhibitors. ..
  27. Epitope-Targeted Vaccine for HIV-1 Prevention
    SUSAN B ZOLLA-PAZNER; Fiscal Year: 2011
    ..Thus, our overall goal is to develop and optimize an immunization regimen that induces long-lasting functional Abs with broad and potent anti-viral activity against HIV-1. ..
  28. SOMATIC MUTATION OF IG VARIABLE REGIONS
    Matthew D Scharff; Fiscal Year: 2013
    ....
  29. Mechanisms that Control IgH Variable Region Exon Assembly
    FREDERICK WAYNE ALT; Fiscal Year: 2013
    ....
  30. Broad-Spectrum Therapeutic Human Antibodies for Dengue Virus Infections
    Yorgo Modis; Fiscal Year: 2006
    ..This project will provide clinicians and public health officials with new means to manage natural, accidental and intentional flavivirus outbreaks. [unreadable] [unreadable] [unreadable]..
  31. AID in somatic mutation of immunoglobulin genes
    URSULA B STORB; Fiscal Year: 2010
    ..This process is beneficial, because it can result in highly specific and efficient antibodies against pathogens and cancer. However, it is also dangerous, because it can cause cancer of lymphocytes and autoimmunity. ..
  32. STRUCTURAL STUDIES OF SUPERANTIGENS
    Douglas Ohlendorf; Fiscal Year: 1999
    ....
  33. DNA repair and lg class switching
    Janet Stavnezer; Fiscal Year: 2007
    ..In Aim 4 we will explore how the mutations are introduced into Ig S regions by determining if the translesion DNA polymerase iota is involved in the error-prone repair of S regions and if this involvement is regulated by cytokines. ..
  34. A humanized transgenic mouse model for studying staphylococcal enterotoxin B
    Chella David; Fiscal Year: 2007
    ..abstract_text> ..
  35. CDK Inhibitor and B Cell Terminal Differentiation
    Selina Chen Kiang; Fiscal Year: 2006
    ..It will also provide a framework for future studies of cell cycle control in B cell immunity, the formation of memory B cells in particular, as well as cell cycle dysregulation in B cell and plasma cell tumorigenesis. ..
  36. CHARACTERIZATION OF AUTOANTIBODIES IN IMMUNE CYTOPENIAS
    Denise Shaw; Fiscal Year: 1992
    ..that autoantibodies produced in each of these diseases originate from limited repertoires of immunoglobulin variable region germline genes, and that such preferential genetic utilization will be reflected by the presence of ..
  37. CELLULAR AND HUMORAL BASES OF MUCOSAL IMMUNE RESPONSE
    JOHN CEBRA; Fiscal Year: 1993
    ..Both allotype congenic immunocompetent and severe combine immunodeficient mice will be used to assess functional potential and protective role of subsets of GC and non-GC PP cells...
  38. SOMATIC DNA RECOMBINATION IN ANTIBODY GENES
    Hitoshi Sakano; Fiscal Year: 1993
    ..They will also shed light on the basic processes of some immunodeficiencies and chromosome abnormalities caused by DNA arrangement...
  39. Biological Definition of FCRL Molecules in Malignancy
    Randall Davis; Fiscal Year: 2009
    ..This work will investigate whether some of these molecules may serve as novel prognostic markers in B-CLL and replace or supplement current indicators of disease aggressiveness. ..
  40. Modulation of Cardiac Mechanics in AL Amyloidosis
    Theodore Abraham; Fiscal Year: 2005
    ..The long-term goal of this research is to better understand the factors that influence the development of cardiac dysfunction in AL with the aim of optimizing treatment strategies to improve clinical outcomes in AL patients. ..
  41. Novel Immunotherapy for Hepatocellular Carcinoma
    Susan Wright; Fiscal Year: 2004
    ..abstract_text> ..
  42. IMMUNOBIOLOGY OF A VIRAL SUPERANTIGEN
    Gary Winslow; Fiscal Year: 1999
    ....
  43. REGULATION OF SURROGATE LIGHT CHAIN IN AGED MICE
    Bonnie Blomberg; Fiscal Year: 2005
    ..The experiments in this proposal will provide a molecular dissection of the abnormal regulation lambda5/VpreB which we hypothesize results in decreased pre-B-cells and an altered VH repertoire in aged mice. ..
  44. ENV DIVERSITY IN SEMEN--HIV PATHOGENESIS IMPLICATIONS
    Nicholas Kartsonis; Fiscal Year: 1999
    ..Support from a K08 research career award will assist in the completion of this proposal and help the applicant realize his career goals. ..
  45. VARIABLE REGION GENE EXPRESSION IN HUMAN AUTOANTIBODIES
    Gregg Silverman; Fiscal Year: 1992
    ..However, the relative contribution of different immunoglobulin variable region genes to autoantibody diversity in patients with autoimmune disease has been difficult to study...
  46. GRSA Proteins in the Diagnosis of Breast Cancer
    WILLIAM NORTH; Fiscal Year: 2002
    ..These methods could be applicable to all patients with breast cancer or suspected breast cancer. ..
  47. ORIGIN OF RHEUMATOID FACTORS
    JAN HILLSON; Fiscal Year: 1993
    ..Data will be analyzed between populations to define relationships in lineage and binding characteristics...
  48. STRATEGIES TO IDENTIFY AND DISTINGUISH FUNGAL PATHOGENS
    RHONDA HONEYCUTT; Fiscal Year: 2000
    ..abstract_text> ..
  49. TARGETED COMPLEMENT INHIBITORS
    Stephen Tomlinson; Fiscal Year: 2003
    ..In addition to therapeutic evaluation, the proposed studies will allow testing of certain hypotheses relating to complement-associated disease mechanisms and the clinical use of complement inhibitors. ..
  50. MECHANISM OF INDUCED PROTECTIVE IMMUNITY IN MURINE CIA
    TARIQ HAQQI; Fiscal Year: 2002
    ..The results obtained are expected to provide novel insight into the mechanisms of induced protective immune responses that may be relevant to the treatment of human rehumatoid arthritis and other autoimmune disorders. ..
  51. INTERACTIONS OF IMMUNOGLOBULINS
    FRED KARUSH; Fiscal Year: 1990
    ..Site- directed mutagenesis will be effected using a primer corresponding to the CDR3 region with nucleotide substitutions designed to provide selected amino-acid replacements...
  52. Novel Innate Immune Receptor in Zebrafish
    GARY LITMAN; Fiscal Year: 2004
    ..Such information is significant to understanding the evolution and interrelatedness of NK and other immune recognition processes. ..
  53. Universal Vectors for the Therapy of Cancer
    MANUEL PENICHET; Fiscal Year: 2005
    ..The training period will also allow me to attend national and international meetings, both expanding my expertise and my network of collaborators and colleagues. ..
  54. B-LYMPHOCYTE MEDIATED IMMUNE MECHANISMS IN ATHEROGENESIS
    Joseph Witztum; Fiscal Year: 2001
    ..These data should provide novel information on T15 B-cell mediated mechanisms in atherogenesis and for the first time characterize "neo-self" ligands to which anti-OxLDL/T15 B cells respond. ..
  55. Role of B-1 Lymphocytes in Athergenesis
    Joseph Witztum; Fiscal Year: 2004
    ..These data should provide novel information on T15 B-cell mediated mechanisms in atherogenesis and for the first time characterize oxidation-specific "neo-self" ligands to which anti-OxLDL/T15 B cells respond...
  56. HUMAN ANTIBODY DIVERSITY IN HEALTH & AUTOIMMUNITY
    Thomas Kipps; Fiscal Year: 1990
    ..Through such studies we may gain a greater appreciation of factors controlling human antibody diversity and insight into host factors that may predispose one to autoimmune disease...
  57. STRATEGY TO DEVELOP IDIOTYPE BASED VACCINES AGAINST HIV
    TRAN CHANH; Fiscal Year: 1992
    ..This multi-project proposal will provide insights into whether idiotype reagents may represent putative vaccine candidates for preventing HIV infection and/or AIDS. ..
  58. ASSEMBLY AND EXPRESSION OF IG VARIABLE REGION GENES
    Frederick Alt; Fiscal Year: 2000
    ....
  59. VACCINE: AUTO-IMMUNE DESTRUCTION OF TRANSPLANTED ISLETS
    Nanette Solvason; Fiscal Year: 1999
    ..If efficacy of the therapeutic vaccine can be demonstrated in late stage pre-diabetic NOD mice, Anergen, Inc., will initiate clinical development of the peptide vaccine against IDDM in humans. ..
  60. PATHOGENESIS OF ANTI-MAG ANTIBODIES IN NEUROPATHY
    Norman Latov; Fiscal Year: 1993
    ..Specifically, the immunoglobulin variable region genes encoding anti-MAG antibodies in different patients will be cloned from hybridoma lines generated ..
  61. SOMATIC MUTATION IN HUMAN B CELLS CULTURED IN VITRO
    Eric Milner; Fiscal Year: 2000
    ..The primary goal of this project is to identify, clone and characterize this T-cell molecule. ..
  62. T CELL LEUKEMIA AND THE HUMAN T CELL ANTIGEN RECEPTOR
    DAVID POSNETT; Fiscal Year: 1991
    ....
  63. Harnessing Somatic Hypermutation for Drug Addiction Research
    HOWARD GU; Fiscal Year: 2009
    ..The cell lines can be used to study many other proteins on their structures, functions, drug binding sites, regulations, etc. ..
  64. Septin 10 Expression Surrogate for IGHV Mutation in CLL
    Weiyi Chen; Fiscal Year: 2005
    ..In Phase II, we plan to validate the correlation in a larger panel of 300 clinically well-characterized CLL patients, and evaluate the impact of this molecular marker in the risk stratification of CLL patients for treatment decisions. ..
  65. ONTOGENY OF THE AUTOIMMUNE B CELL REPERTOIRE IN MAN
    Leonard Stein; Fiscal Year: 1992
    ....
  66. In vivo imaging and therapeutic efficacy of NSC-secreted nanobodies
    Khalid Shah; Fiscal Year: 2009
    ..The developed agents and strategies will be designed to be clinically translatable and should have a major impact in developing efficient therapies for brain tumors. ..