Genomes and Genes
Gene Symbol: Rag2
Description: recombination activating gene 2
Alias: Rag-2, V(D)J recombination-activating protein 2, recombinase activating gene 2, recombination activating protein 2
Publications150 found, 100 shown here
- Overlapping signals for protein degradation and nuclear localization define a role for intrinsic RAG-2 nuclear uptake in dividing cellsAshley E Ross
Department of Molecular Biology and Genetics and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, 725 N Wolfe Street, Baltimore, MD 21205, USA
Mol Cell Biol 23:5308-19. 2003..These results suggest that the intrinsic RAG-2 NLS functions in the nuclear uptake of RAG-2 following its reexpression in cycling cells...
- Identification of a third evolutionarily conserved gene within the RAG locus and its RAG1-dependent and -independent regulationMalgorzata Cebrat
Department of Tumor Immunology, Laboratory of Transgenesis and Lymphocyte Biology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
Eur J Immunol 35:2230-8. 2005Recombination-activating gene (RAG)1 and RAG2 encode T and B lymphocyte-specific endonucleases indispensable for rearrangements of antigen-receptor gene segments but also capable of causing deleterious chromosome rearrangements...
- Foxo1 directly regulates the transcription of recombination-activating genes during B cell developmentRupesh H Amin
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA
Nat Immunol 9:613-22. 2008..Foxo1 directly activated transcription of the Rag1-Rag2 locus throughout early B cell development, and a decrease in Foxo1 protein diminished the induction of Rag1 and ..
- RAG-1-deficient mice have no mature B and T lymphocytesP Mombaerts
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139
Cell 68:869-77. 1992..Although RAG-1 expression has been reported in the central nervous system of the mouse, no obvious neuroanatomical or behavioral abnormalities have been found in the RAG-1-deficient mice...
- RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangementY Shinkai
Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032
Cell 68:855-67. 1992..Because the SCID phenotype was the only obvious abnormality detected in RAG-2 mutant mice, RAG-2 function and V(D)J recombinase activity, per se, are not required for development of cells other than lymphocytes...
- RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombinationM A Oettinger
Whitehead Institute for Biomedical Research, Cambridge, MA 02142
Science 248:1517-23. 1990..RAG-1 and RAG-2 might activate the expression of the V(D)J recombinase but, more likely, they directly participate in the recombination reaction...
- Cutting edge: basophils are transiently recruited into the draining lymph nodes during helminth infection via IL-3, but infection-induced Th2 immunity can develop without basophil lymph node recruitment or IL-3Sohee Kim
Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
J Immunol 184:1143-7. 2010..Our results reveal a previously unknown role of IL-3 in recruiting basophils to the LN and demonstrate that basophils are not necessarily associated with the development of Th2 immunity during parasite infection...
- Thymic emigration revisitedTom M McCaughtry
Center for Immunology, Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455
J Exp Med 204:2513-20. 2007..Furthermore, emigration occurs via a strict "conveyor belt" mechanism, where the oldest thymocytes leave first...
- Positive selection through a motif in the alphabeta T cell receptorB T Backstrom
Basel Institute for Immunology, CH 4005 Basel, Switzerland
Science 281:835-8. 1998..Thus, the alpha-CPM seems to participate in the generation of signals required for positive selection...
- No requirement for V(D)J recombination in p53-deficient thymic lymphomaM J Liao
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill Medical School, Chapel Hill, North Carolina 27599, USA
Mol Cell Biol 18:3495-501. 1998....
- CTLA-4 regulates induction of anergy in vivoR J Greenwald
Immunology Research Division, Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, 02115, USA
Immunity 14:145-55. 2001..Thus, CTLA-4 has an essential role in determining the outcome of T cell encounter with a tolerogenic stimulus...
- The RAG2 C terminus suppresses genomic instability and lymphomagenesisLudovic Deriano
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
Nature 471:119-23. 2011Misrepair of DNA double-strand breaks produced by the V(D)J recombinase (the RAG1/RAG2 proteins) at immunoglobulin (Ig) and T cell receptor (Tcr) loci has been implicated in pathogenesis of lymphoid malignancies in humans and in mice...
- Adaptive immunity maintains occult cancer in an equilibrium stateCatherine M Koebel
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
Nature 450:903-7. 2007..These results reveal that, in addition to destroying tumour cells and sculpting tumour immunogenicity, the immune system of a naive mouse can also restrain cancer growth for extended time periods...
- Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancyA A Ashkar
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1
J Exp Med 192:259-70. 2000....
- Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4(+) T cellsLie Wang
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Nat Immunol 9:1122-30. 2008..We propose that GATA-3 acts as a specification factor for the CD4(+) lineage 'upstream' of the ThPOK-controlled CD4(+) commitment checkpoint...
- Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cellsKatsuto Takenaka
Division of Cellular and Molecular Biology, University Health Network, Toronto, Ontario M5G2M9, Canada
Nat Immunol 8:1313-23. 2007..Thus, we have identified Sirpa polymorphism as a potent genetic determinant of the engraftment of human hematopoietic stem cells...
- Quantitative assessment of human T lymphocytes in RAG2(-/-)gammac(-/-) mice: the impact of ex vivo manipulation on in vivo functionalityRozemarijn S van Rijn
Jordan Laboratory for Hemato Oncology, Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands
Exp Hematol 35:117-27. 2007..In this study, we investigated the feasibility of using the huPBMC- RAG2(-/-)gammac(-/-) xenogeneic mouse model...
- T-bet plays a key role in NK-mediated control of melanoma metastatic diseaseMiriam B F Werneck
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
J Immunol 180:8004-10. 2008..Taken together, these results show for the first time an irreplaceable role for T-bet in the NK-mediated cross-talk between innate and adaptive immune responses to metastatic disease...
- Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lungTim Willinger
Department of Immunobiology, The Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 108:2390-5. 2011..The hIL-3/GM-CSF KI mice represent a unique mouse model that permits the study of human mucosal immune responses to lung pathogens...
- The distal V(H) gene cluster of the Igh locus contains distinct regulatory elements with Pax5 transcription factor-dependent activity in pro-B cellsAnja Ebert
Research Institute of Molecular Pathology, Vienna Biocenter, Dr Bohr Gasse 7, Vienna, Austria
Immunity 34:175-87. 2011..The pro-B cell-specific and Pax5-dependent activity of the PAIR elements suggests that they are involved in the regulation of distal V(H)-DJ(H) recombination at the Igh locus...
- The recombination activating gene-1 (RAG-1) transcript is present in the murine central nervous systemJ J Chun
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142
Cell 64:189-200. 1991..The results suggest that RAG-1 functions in neurons, where its role might be to recombine elements of the neuronal genome site-specifically, or to prevent detrimental alterations of the genome in these long-lived cells...
- Commitment to the B-lymphoid lineage depends on the transcription factor Pax5S L Nutt
Research Institute of Molecular Pathology, Vienna, Austria
Nature 401:556-62. 1999..Pax5 therefore plays an essential role in B-lineage commitment by suppressing alternative lineage choices...
- A conserved degradation signal regulates RAG-2 accumulation during cell division and links V(D)J recombination to the cell cycleZ Li
Department of Molecular Biology and Genetics, John Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Immunity 5:575-89. 1996..Using transgenic mice expressing the T490A RAG-2 mutant and a functional T cell receptor beta chain, we demonstrate that coupling of V(D)J recombination to the cell cycle is not essential for enforcement of allelic exclusion...
- Influence of immunoglobulin heavy- and light-chain expression on B-cell differentiationF Young
Howard Hughes Medical Institute, Children s Hospital, Boston, Massachusetts 02115
Genes Dev 8:1043-57. 1994....
- The V(D)J recombination activating gene, RAG-1D G Schatz
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142
Cell 59:1035-48. 1989..RAG-1 may activate V(D)J recombination indirectly, or it may encode the V(D)J recombinase itself...
- An improved model to study tumor cell autonomous metastasis programs using MTLn3 cells and the Rag2(-/-) gammac (-/-) mouseSylvia E Le Dévédec
Division of Toxicology, Leiden Amsterdam Center for Drug Research LACDR, Leiden University, RA, Leiden, The Netherlands
Clin Exp Metastasis 26:673-84. 2009..Using the highly metastatic EGFR-overexpressing MTLn3 cell-line, we report that only Rag2(-/-)gammac(-/-) mice, which lack NK cells, allow efficient lung metastasis from primary tumors in the mammary gland...
- CX3CR1 defines functionally distinct intestinal mononuclear phagocyte subsets which maintain their respective functions during homeostatic and inflammatory conditionsBenjamin Weber
Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland
Eur J Immunol 41:773-9. 2011..CX3CR1(+) iMNP can further be subdivided based on differential expression of CX3CR1. Using CX3CR1(GFP/+) ×RAG2(-/-) mice, we demonstrate that CX3CR1(hi) and CX3CR1(lo) iMNP clearly differ with respect to their morphological ..
- B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitorsLisa Borghesi
Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester 01655, USA
J Exp Med 199:491-502. 2004..Evidence of this recombinase activity is detectable in all four progeny lineages (B, T, and NK, and DC), and rag2 levels are the highest in progenitor subsets immediately downstream of the CLP...
- Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell developmentStephen Malin
Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria
Nat Immunol 11:171-9. 2010..Hence, STAT5 and IL-7 signaling control cell survival and the developmental ordering of immunoglobulin gene rearrangements by suppressing premature Igk recombination in pro-B cells...
- Osteoclast-derived matrix metalloproteinase-7, but not matrix metalloproteinase-9, contributes to tumor-induced osteolysisSophie Thiolloy
Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, USA
Cancer Res 69:6747-55. 2009..Our studies indicate that the selective inhibition of MMP-7 in the tumor-bone microenvironment may be of benefit for the treatment of lytic breast-to-bone metastases...
- Cancer immunoediting of the NK group 2D ligand H60aTimothy O'Sullivan
Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA
J Immunol 187:3538-45. 2011..In one of these cell lines, the H60a-hi cells could be removed by passaging the cells through RAG2(-/-) mice, resulting in edited cell lines that were poor targets for NK cells and that displayed progressive tumor ..
- IL-2 receptor alpha chain expression during early B lymphocyte differentiationJ Chen
Howard Hughes Medical Institute, Boston, MA
Int Immunol 6:1265-8. 1994..Its potential function in early B cell differentiation is discussed in comparison with its role in thymocyte differentiation...
- Complexity of transcriptional regulation within the Rag locus: identification of a second Nwc promoter region within the Rag2 intronAgnieszka Laszkiewicz
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
Immunogenetics 63:183-7. 2011..Here, we analyzed the phenotype of Nwc(tmpro1) mice, in which the Rag2 intragenic region containing the previously identified promoter responsible for initiating transcription of Nwc in ..
- A regulatory role for recombinase activating genes, RAG-1 and RAG-2, in T cell developmentJ Wayne
Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021
Immunity 1:95-107. 1994..We propose that in addition to a previously documented role in V(D)J recombination, RAG-1 and RAG-2 expression must be properly regulated for completion of normal T cell development..
- The gene encoding early growth response 2, a target of the transcription factor NFAT, is required for the development and maturation of natural killer T cellsVanja Lazarevic
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
Nat Immunol 10:306-13. 2009..We found that Egr2 was important in the selection, survival and maturation of NKT cells. Our findings emphasize the importance of the calcineurin-NFAT-Egr2 pathway in the development of the NKT lymphocyte lineage...
- The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor lociYanhong Ji
Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, Box 208011, New Haven, CT 06520 8011, USA
Cell 141:419-31. 2010The critical initial step in V(D)J recombination, binding of RAG1 and RAG2 to recombination signal sequences flanking antigen receptor V, D, and J gene segments, has not previously been characterized in vivo...
- The IL-7 signaling pathway regulates lymph node development independent of peripheral lymphocytesStephane Chappaz
Department of Biomedicine, University of Basel, Basel, Switzerland
J Immunol 184:3562-9. 2010..of thymic stromal lymphopoietin (TSLP) increased LTi cell numbers and restored LN development in IL-7(-/-) and RAG2(-/-) gamma(c)(-/-) mice...
- RAG2's non-core domain contributes to the ordered regulation of V(D)J recombinationJohn D Curry
Division of Immunology, Department of Molecular and Cell Biology, University of California at Berkeley, 439 Life Sciences Addition, Berkeley, CA 94720 3200, USA
Nucleic Acids Res 36:5750-62. 2008..In mice lacking the non-core domain of RAG2 the ordered rearrangement is disturbed and direct V to D rearrangements are 10- to 1000-times increased in tri-..
- IL-7 Is essential for the development and the persistence of chronic colitisTeruji Totsuka
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
J Immunol 178:4737-48. 2007....
- Mechanism of lymphocyte-specific inactivation of RAG-2 intragenic promoter of NWC: implications for epigenetic control of RAG locusMalgorzata Cebrat
Department of Tumor Immunology, Institute of Immunology and Experimental Therapy, Weigla 12, 53 114 Wroclaw, Poland
Mol Immunol 45:2297-306. 2008..The implications of our findings for understanding mechanisms regulating transcription within RAG/NWC locus in different cells are discussed and the model of epigenetic control of this locus is proposed...
- Cutting Edge: a thymocyte-thymic epithelial cell cross-talk dynamically regulates intrathymic IL-7 expression in vivoNuno L Alves
Cytokines and Lymphoid Development Unit, Institut Pasteur, Paris, France
J Immunol 184:5949-53. 2010..Although Il7(+) TECs normally diminish with age, we found that Il7(+) TECs are markedly retained in alymphoid Rag2(-/-)Il2rg(-/-) IL-7 reporter mice that manifest a profound thymopoietic arrest...
- Conventional T-bet(+)Foxp3(-) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infectionDragana Jankovic
Immunobiology Section and 2Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
J Exp Med 204:273-83. 2007..These findings indicate that IL-10 production by CD4(+) T lymphocytes need not involve a distinct regulatory Th cell subset but can be generated in Th1 cells as part of the effector response to intracellular pathogens...
- Roles for common cytokine receptor gamma-chain-dependent cytokines in the generation, differentiation, and maturation of NK cell precursors and peripheral NK cells in vivoChristian A J Vosshenrich
Unité des Cytokines et Développement Lymphoide, Institut Nationale de la Santé et Recherche Médicale Equipe 101, Institut Pasteur, Paris, France
J Immunol 174:1213-21. 2005..Surprisingly, the few residual NK cells generated in absence of IL-15 appear relatively mature, expressing a variety of Ly49 receptors and demonstrating lytic and cytokine production capacity...
- Elimination of colon cancer in germ-free transforming growth factor beta 1-deficient miceSandra J Engle
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267 0524, USA
Cancer Res 62:6362-6. 2002..This animal model should provide insight into the protective role of TGF-beta1 in early stages of ulcerative colitis-associated human colon cancer...
- RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin lociSusannah L Hewitt
Department of Pathology, New York University School of Medicine, New York, New York, USA
Nat Immunol 10:655-64. 2009..ATM activated by the cleaved allele acts in trans on the uncleaved allele to prevent biallelic recombination and chromosome breaks or translocations...
- Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alphaD A Fruman
Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Science 283:393-7. 1999..Lymphocyte development and function was studied with the use of the RAG2-deficient blastocyst complementation system...
- Chimeric IgH-TCRalpha/delta translocations in T lymphocytes mediated by RAGElsa Callen
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Cell Cycle 8:2408-12. 2009..We suggest a new model for how oncogenic translocations can arise from two non-concerted physiological DSBs...
- Opposing regulation of T cell function by Egr-1/NAB2 and Egr-2/Egr-3Sam Collins
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
Eur J Immunol 38:528-36. 2008..Overall, our data suggest that just as the Egr/NAB network of genes control cell fate in other systems, TCR-induced Egr-1, 2, 3 and NAB2 control the fate of antigen recognition in T cells...
- Characterization of chromatin structure and enhancer elements for murine recombination activating gene-2Xing Cheng Wei
Department of Immunology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan
J Immunol 169:873-81. 2002..These results show that the tissue- and stage-specific expression of murine RAG-2 is regulated by alteration of the chromatin structure as well as cis-regulatory enhancer elements...
- Interleukin 7 receptor control of T cell receptor gamma gene rearrangement: role of receptor-associated chains and locus accessibilityS K Durum
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, Maryland 21702, USA
J Exp Med 188:2233-41. 1998..This data supports the model that IL-7R promotes TCR-gamma gene rearrangement by regulating accessibility of the locus via demethylation and histone acetylation of the locus...
- CD8+ T cells maintain tolerance to myelin basic protein by 'epitope theft'Antoine Perchellet
Department of Immunology, University of Washington, Box 357650, Seattle, Washington 98195, USA
Nat Immunol 5:606-14. 2004..This form of immune regulation could limit responses of self-reactive T cells that escape other tolerance mechanisms...
- Two distinct steps during thymocyte maturation from CD4-CD8- to CD4+CD8+ distinguished in the early growth response (Egr)-1 transgenic mice with a recombinase-activating gene-deficient backgroundT Miyazaki
Basel Institute for Immunology, Postfach CH 4005, Basel, Switzerland
J Exp Med 186:877-85. 1997..The first step, from the CD25+CD44- DN to the ISP stage, can be entirely promoted by overexpression of Egr-1...
- B-Raf-mediated signaling pathway regulates T cell developmentHirotake Tsukamoto
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
Eur J Immunol 38:518-27. 2008..In conclusion, we present first evidence for the important role of B-Raf-mediated signaling in T cell development...
- A 220-nucleotide deletion of the intronic enhancer reveals an epigenetic hierarchy in immunoglobulin heavy chain locus activationTirtha Chakraborty
Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
J Exp Med 206:1019-27. 2009..These observations define Emu-independent and Emu-dependent phases of locus activation that reveal an unappreciated epigenetic hierarchy in tissue-specific gene expression...
- Impact of negative selection on the T cell repertoire reactive to a self-peptide: a large fraction of T cell clones escapes clonal deletionC Bouneaud
Unité de Biologie Moléculaire du Gène, INSERM U277, Institut Pasteur, Paris, France
Immunity 13:829-40. 2000..These results suggest that numerous low-affinity self-specific T cells persist in the periphery and show that a deleting ligand can specifically narrow the structural diversity of the TCR repertoire...
- A non-B-DNA structure at the Bcl-2 major breakpoint region is cleaved by the RAG complexSathees C Raghavan
Norris Comprehensive Cancer Center, Room 5428, University of Southern California Keck School of Medicine, 1441 Eastlake Ave, MC9176, Los Angeles, California 90033, USA
Nature 428:88-93. 2004..Hence, a stable non-B-DNA structure in the human genome appears to be the basis for the fragility of the Bcl-2 Mbr, and the RAG complex is able to cleave this structure...
- Role of the individual interferon systems and specific immunity in mice in controlling systemic dissemination of attenuated pseudorabies virus infectionP Grob
Institute of Virology, University of Zurich, CH 8057 Zurich, Switzerland
J Virol 73:4748-54. 1999..We present evidence that mice with an intact gamma IFN system but without mature B and T cells were able to prevent systemic dissemination of gE-TK-PRV...
- A direct interaction between the RAG2 C terminus and the core histones is required for efficient V(D)J recombinationKelly L West
Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029, USA
Immunity 23:203-12. 2005..Here, we report that RAG2 binds directly to the core histone proteins...
- The loss of PTEN allows TCR alphabeta lineage thymocytes to bypass IL-7 and Pre-TCR-mediated signalingThijs J Hagenbeek
Department of Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands
J Exp Med 200:883-94. 2004..Analysis of mice deficient for Pten and CD3gamma; Pten and gammac; or Pten, gammac, and Rag2 revealed that deletion of PTEN can substitute for both IL-7 and pre-TCR signals...
- Elucidation of IgH intronic enhancer functions via germ-line deletionThomas Perlot
The CBR Institute for Biomedical Research, Inc, and Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 102:14362-7. 2005..The availability of mice with the iEmu mutation in their germ line will facilitate future studies to elucidate the roles of iEmu in V(H)(D)J(H) recombination in the context of IgH chromatin structure and germ-line transcription...
- Regulation of IgH gene assembly: role of the intronic enhancer and 5'DQ52 region in targeting DHJH recombinationRoshi Afshar
Department of Microbiology Immunology, Vanderbilt University Medical School, Nashville, TN 37232, USA
J Immunol 176:2439-47. 2006....
- Coordinate regulation of RAG1 and RAG2 by cell type-specific DNA elements 5' of RAG2W Yu
Laboratory of Molecular Immunology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Science 285:1080-4. 1999RAG1 and RAG2 are essential for V(D)J recombination and lymphocyte development. These genes are thought to encode a transposase derived from a mobile genetic element that was inserted into the vertebrate genome 450 million years ago...
- Toll-like receptor 7-dependent loss of B cell tolerance in pathogenic autoantibody knockin miceRobert Berland
Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
Immunity 25:429-40. 2006..These results demonstrate that the particular threat of nucleic acid-containing autoantigens lies in their ability to bind both antigen receptor and TLR7...
- Roles for NBS1 in alternative nonhomologous end-joining of V(D)J recombination intermediatesLudovic Deriano
Department of Pathology, The Helen L and Martin S Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine and, New York University School of Medicine, New York, NY 10016, USA
Mol Cell 34:13-25. 2009..These data demonstrate that the MRE11 complex functions at two distinct levels, regulating repair pathway choice (likely through enhancing the stability of DNA end complexes) and participating in alternative NHEJ of coding ends...
- A plant homeodomain in RAG-2 that binds Hypermethylated lysine 4 of histone H3 is necessary for efficient antigen-receptor-gene rearrangementYun Liu
Department of Molecular Biology and Genetics, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Immunity 27:561-71. 2007..Together, these findings are consistent with the interpretation that recognition of hypermethylated histone H3 K4 promotes efficient V(D)J recombination in vivo...
- Development of regulatory T cells requires IL-7Ralpha stimulation by IL-7 or TSLPRenata Mazzucchelli
Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute NCI, National Institutes of Health NIH, Frederick, MD, USA
Blood 112:3283-92. 2008....
- Rag mutations reveal robust alternative end joiningBarbara Corneo
The Kimmel Center for Biology and Medicine of the Skirball Institute and Department of Pathology, New York University School of Medicine, New York, New York 10016, USA
Nature 449:483-6. 2007..mechanism for generating diversity in antigen receptors, relies on NHEJ for repairing DSBs introduced by the Rag1-Rag2 protein complex. Animals lacking any of the seven known NHEJ factors are therefore immunodeficient...
- Chromosomal reinsertion of broken RSS ends during T cell developmentJohn D Curry
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
J Exp Med 204:2293-303. 2007..wild-type, p53, p53 x scid, H2Ax, and ATM mutant thymocytes all showed similar levels of RSS end insertions, core-RAG2 mutant thymocytes showed a sevenfold greater frequency of such events...
- The RhoA transcriptional program in pre-T cellsM Mullin
Samuel Lunenfeld Research Institute, 600 University Avenue, Toronto, Ontario, Canada
FEBS Lett 581:4309-17. 2007..causes a developmental block that pheno-copies the consequence of losing pre-TCR expression in Recombinase gene 2 (Rag2) null mice...
- Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transitionChangchuin Mao
Molecular Oncology Research Institute, Tufts New England Medical Center, 750 Washington Street, Boston, MA 02111, USA
J Immunol 178:5443-53. 2007..Akt1 and Akt2 also contribute to the differentiation process by promoting the survival of the DP thymocytes...
- Pre-B cell receptor-mediated cell cycle arrest in Philadelphia chromosome-positive acute lymphoblastic leukemia requires IKAROS functionDaniel Trageser
Leukemia and Lymphoma Program, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90027, USA
J Exp Med 206:1739-53. 2009....
- ATM prevents the persistence and propagation of chromosome breaks in lymphocytesElsa Callen
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1360, USA
Cell 130:63-75. 2007..Silencing this checkpoint permits DNA ends produced by V(D)J recombination in a lymphoid precursor to serve as substrates for translocations with chromosomes subsequently damaged by other means in mature cells...
- Continued RAG expression in late stages of B cell development and no apparent re-induction after immunizationW Yu
Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10021, USA
Nature 400:682-7. 1999..mice carrying a bacterial artificial chromosome that encodes a green fluorescent protein reporter instead of RAG2. We find that the reporter is expressed in all immature B cells in the bone marrow and spleen...
- Localization, interaction, and RNA binding properties of the V(D)J recombination-activating proteins RAG1 and RAG2E Spanopoulou
Rockefeller University, New York, New York 10021, USA
Immunity 3:715-26. 1995The RAG1 and RAG2 gene products are indispensable for activating somatic rearrangement of antigen receptor gene segments. The two proteins form a stable complex in primary thymocytes as well as when expressed in adherent cells...
- Deletion of the RAG2 C terminus leads to impaired lymphoid development in miceYoshiko Akamatsu
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
Proc Natl Acad Sci U S A 100:1209-14. 2003The recombination-activating gene (RAG)1 and RAG2 proteins comprise the lymphocyte-specific components of the V(D)J recombinase and are required for the assembly of antigen-receptor variable-region genes...
- PU.1 regulates expression of the interleukin-7 receptor in lymphoid progenitorsRodney P DeKoter
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, 5841 S Maryland Ave, MC1028, Chicago, IL 60637, USA
Immunity 16:297-309. 2002..1 in early B cell development, it is not required. These results demonstrate that PU.1 functions to regulate early B cell development in part by controlling the expression of the IL-7Ralpha gene...
- Enhanced human cell engraftment in mice deficient in RAG2 and the common cytokine receptor gamma chainJ P Goldman
Molecular Immunology Unit, Institute of Child Health, London, UK
Br J Haematol 103:335-42. 1998..A genetic cross with a recombinase activating gene 2 (RAG2)-deficient strain produced mice doubly homozygous for the gamma c and RAG2 null alleles (gamma c-..
- Modulation of the IL-7 dose-response threshold during pro-B cell differentiation is dependent on pre-B cell receptor expressionA J Marshall
Ontario Cancer Institute and Department of Immunology, University of Toronto, Canada
J Immunol 161:6038-45. 1998..Our results suggest that positive selection of pre-BCR+ pro-B cells may be achieved through the fine tuning of IL-7 responses...
- Increased accumulation of hybrid V(D)J joins in cells expressing truncated versus full-length RAGsJ A Sekiguchi
Howard Hughes Medical Institute, Harvard University Medical School, Boston, MA 02115, USA
Mol Cell 8:1383-90. 2001RAG1 and RAG2 (RAGs) initiate V(D)J recombination by introducing breaks between two coding segments and flanking recombination signals (RSs). Nonhomologous end-joining (NHEJ) proteins then join the coding segments and join the RSs...
- Cell-fate decisions in early T cell development: regulation by cytokine receptors and the pre-TCRM C Haks
Division of Immunology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Plesmanlaan 121, Amsterdam, CX, 1066, The Netherlands
Semin Immunol 11:23-37. 1999....
- Induction of pre-B cell proliferation after de novo synthesis of the pre-B cell receptorJ Hess
Institut für Medizinische Strahlenkunde und Zellforschung MSZ, University of Wurzburg, Versbacher Strasse 5, D 97078 Wurzburg, Germany
Proc Natl Acad Sci U S A 98:1745-50. 2001..We conclude that pre-BCR signaling induces clonal expansion of early pre-B cells...
- Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivoN C Fernandez
Departement de Biologie Clinique, Institut Gustave Roussy, Villejuif, France
Nat Med 5:405-11. 1999..Thus, DC are involved in the interaction between innate and adaptive immune responses...
- Recombinase-activating gene (RAG) 2-mediated V(D)J recombination is not essential for tumorigenesis in Atm-deficient miceL K Petiniot
Experimental Immunology Branch, Genetics Department, Biostatistics and Data Management Section, Office of the Director of the Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Proc Natl Acad Sci U S A 97:6664-9. 2000..Since V(D)J recombination is a recombinase-activating gene (RAG)-dependent process, we generated Rag2(-/-)Atm(-/-) mice to assess the requirement for RAG-dependent recombination in thymic lymphomagenesis...
- B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signalsF Loder
Department of Molecular Immunology, University of Freiburg, Germany
J Exp Med 190:75-89. 1999....
- RAG2:GFP knockin mice reveal novel aspects of RAG2 expression in primary and peripheral lymphoid tissuesR J Monroe
Howard Hughes Medical Institute, The Children s Hospital, The Center for Blood Research and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
Immunity 11:201-12. 1999We generated mice in which a functional RAG2:GFP fusion gene is knocked in to the endogenous RAG2 locus...
- The earliest T lineage-committed cells depend on IL-7 for Bcl-2 expression and normal cell cycle progressionU von Freeden-Jeffry
Department of Immunobiology, DNAX Research Institute, Palo Alto, California 94304, USA
Immunity 7:147-54. 1997..These data specify a T cell lineage developmental transition point, prior to T cell antigen receptor rearrangement, where IL-7 signal transduction is linked to an anti-apoptosis mechanism and the cell cycle...
- Cell cycle regulation of V(D)J recombination-activating protein RAG-2W C Lin
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205
Proc Natl Acad Sci U S A 91:2733-7. 1994..The variation in RAG-2 protein is likely to be established, at least in part, by a posttranscriptional mechanism. These observations suggest that V(D)J rearrangement occurs entirely or preferentially within G0/G1...
- Restoration of T cell development in RAG-2-deficient mice by functional TCR transgenesY Shinkai
Howard Hughes Medical Institute, Children s Hospital, Boston, MA 02115
Science 259:822-5. 1993..RAG-2-/- mice that expressed alpha and beta TCR transgenes developed both DP and single positive thymocytes. Thus, the TCR beta subunit, possibly in association with a novel CD3 complex, participates in the DN to the DP transition...
- Essential role of LAT in T cell developmentW Zhang
Section on Lymphocyte Signaling, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
Immunity 10:323-32. 1999..Intrathymic development was blocked within the CD4- CD8- stage. No gross abnormality of NK or platelet function was observed. LAT is thus critical to both T cell activation and development...
- T cell receptor-independent basal signaling via Erk and Abl kinases suppresses RAG gene expressionJeroen P Roose
Department of Medicine, University of California, San Francisco, USA
PLoS Biol 1:E53. 2003..Our data suggest that physiologic gene expression programs depend upon tonic activity of signaling pathways independent of receptor ligation...
- A conserved transcriptional enhancer regulates RAG gene expression in developing B cellsLih Yun Hsu
Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
Immunity 19:105-17. 2003Although expression of the RAG1 and RAG2 genes is essential for lymphocyte development, the mechanisms responsible for the lymphoid- and developmental stage-specific regulation of these genes are poorly understood...
- DNA sequence and structure requirements for cleavage of V(D)J recombination signal sequencesC A Cuomo
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell Biol 16:5683-90. 1996Purified RAG1 and RAG2 proteins can cleave DNA at V(D)J recombination signals...
- Down-regulation of RAG1 and RAG2 gene expression in preB cells after functional immunoglobulin heavy chain rearrangementU Grawunder
Basel Institute for Immunology, Switzerland
Immunity 3:601-8. 1995..The gene products of two recombination activating genes, RAG1 and RAG2 are crucial for this rearrangement process...
- Intradermal administration of thymic stromal lymphopoietin induces a T cell- and eosinophil-dependent systemic Th2 inflammatory responseHeidi K Jessup
Inflammation Research, Amgen, Seattle, WA 98119, USA
J Immunol 181:4311-9. 2008..TSLP-induced responses were significantly, but not completely reduced in IL-4- and IL-13-deficient mice. These results shed light on the pathways and cell types involved in TSLP-induced inflammation...
- T cell receptor contact to restricting MHC molecules is a prerequisite for peripheral interclonal T cell competitionFabien Agenes
Institut National de la Santé et de la Recherche Médicale U548, Grenoble, Cedex 9, France
J Exp Med 205:2735-43. 2008..This mechanism allows a local competitiveness that extends beyond a T cell's specificity...
- Impaired expansion of mouse B cell progenitors lacking BtkJ D Kerner
Department of Immunology, University of Washington, Seattle 98195, USA
Immunity 3:301-12. 1995..a targeted disruption of the btk gene and examined their potential to produce lymphocytes in both C57BL/6 and RAG2-/- host chimeric animals...
- Bystander activation of cytotoxic T cells: studies on the mechanism and evaluation of in vivo significance in a transgenic mouse modelS Ehl
Institute of Experimental Immunology, Department of Pathology, University of Zurich, Switzerland
J Exp Med 185:1241-51. 1997..We conclude that although bystander activation via cytokines may generate cytolytically active CTL from naive precursors, quantitative considerations suggest that this is usually not of major biological consequence...
- Deletion of Shp2 tyrosine phosphatase in muscle leads to dilated cardiomyopathy, insulin resistance, and premature deathFrederic Princen
Burnham Institute for Medical Research, 10901 N Torrey Pines Rd, La Jolla, CA 92037, USA
Mol Cell Biol 29:378-88. 2009....
- CTCF regulates cell cycle progression of alphabeta T cells in the thymusHelen Heath
Department of Cell Biology and Genetics, Erasmus MC, Rotterdam, The Netherlands
EMBO J 27:2839-50. 2008..We propose that CTCF positively regulates cell growth in rapidly dividing thymocytes so that appropriate number of cells are generated before positive and negative selection in the thymus...
- T cells, but not B cells, are required for bowel inflammation in interleukin 2-deficient miceA Ma
Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115, USA
J Exp Med 182:1567-72. 1995..IL-2-/-, JH-/- mice do not, however, succumb to anemia. Thus, spontaneous intestinal inflammation in IL-2-/- mice requires mature T cells, not B cells, while anemia is dependent on B cells...
- Development of CD4+CD8+ thymocytes in RAG-deficient mice through a T cell receptor beta chain-independent pathwayC J Guidos
Division of Immunology and Cancer, Hospital for Sick Children Research Institute, Toronto, Canada
J Exp Med 181:1187-95. 1995..These results suggest an in vivo pathway for DP thymocyte development which is TCR beta chain independent...
- An Animal Model of Hemophagocytic LymphohistiocytosisMichael Jordan; Fiscal Year: 2009..This project will lead to better understanding of how cytotoxic function regulates the immune response and lead to improved therapies for patients with HLH and perhaps many other immunopathologic disorders. ..
- Role of IL10 and TGFb1 in colon cancerSusan E Erdman; Fiscal Year: 2010..We propose to build upon our recent scientific breakthroughs and test strategies in mice that will stimulate potent and highly beneficial Treg to prevent cancer and impart healthful longevity in humans. ..
- Role of IL10 and TGFb1 in colon cancerSUSAN ERDMAN; Fiscal Year: 2007..Information gained from these studies may elucidate pivotal mechanisms and uncover novel strategies for prevention and treatment of human colon cancer. ..
- The role of T-cells and Th 1 immunity in cholesterol gallstonesKIRK MAURER; Fiscal Year: 2007..To accomplish this aim T cell subsets (effector T-cells and regulatory T cells) will be transferred to Rag 2-/- mice...
- An Animal Model of Hemophagocytic LymphohistiocytosisMichael Jordan; Fiscal Year: 2007..This project will lead to better understanding of how cytotoxic function regulates the immune response and lead to improved therapies for patients with HLH and perhaps many other immunopathologic disorders. ..
- CIS-REGULATORY ANALYSIS OF PU.1 BY IN VITRO ES CELL DIFFERENTIATIONELLEN ROTHENBERG; Fiscal Year: 2007..This should permit faster and cheaper experiments to reveal how powerful regulatory genes are themselves controlled. ..
- Clonal analysis of joint-infiltrating natural Killer cells in chronic arthritisLisa Borghesi; Fiscal Year: 2007..Characterizing the developmental dynamics and functional activities of recombination* inflammatory NK cells could provide insights into the development of alternative therapies for RA. ..
- Mouse Models of Tumor Progression and Therapy ResponseCHRISTOPHER KEMP; Fiscal Year: 2007..These experiments will reveal the molecular and cellular basis for the poor clinical outcome associated with p27 deficient tumors. This knowledge can then be applied to improve treatment design and regimen in the clinical setting. ..
- Experimental transfusion-related acute lung injuryMark Looney; Fiscal Year: 2007..Looney, and at the end of the grant period, Dr. Looney will be well equipped to embark on a successful career as an independent investigator in the field of acute lung injury. (End of Abstract) ..
- GATA-3 in precursor commitment to the T lineageELLEN ROTHENBERG; Fiscal Year: 2007..Definition of mechanistic requirements for GATA-3 perturbation of T-cell development 3. Attempted rescue of GATA-3 overexpression effects by cotransduction with targets of specific repression ..
- ANALYSIS OF THE MURINE ANTIBODY REPERTOIREGarnett Kelsoe; Fiscal Year: 2007..These immature cells proliferate and express the RAG2 recombinase protein but not BCL-6, a trans- criptional repressor thought to be absolutely required for the GC ..
- An Animal Model of Hemophagocytic LymphohistiocytosisMichael Jordan; Fiscal Year: 2010..This project will lead to better understanding of how cytotoxic function regulates the immune response and lead to improved therapies for patients with HLH and perhaps many other immunopathologic disorders. ..
- B-cell Tolerance and Humoral Immunity to HIV-1GARNETT H KELSOE; Fiscal Year: 2010..abstract_text> ..
- ANALYSIS OF THE MURINE ANTIBODY REPERTOIREGARNETT H KELSOE; Fiscal Year: 2010..Qom cap mop axiom 0-c 0opccc woo'- t00 0co -td ..
- An Animal Model of Hemophagocytic LymphohistiocytosisMichael Jordan; Fiscal Year: 2010
- Mechanisms of Pulmonary Mast Cell Recruitment and MaturationMichael Gurish; Fiscal Year: 2010....
- LINEAGE COMMITMENT MECHANISMS IN LYMPHOID PRECURSORSEllen V Rothenberg; Fiscal Year: 2010..The mechanisms studied here imply that mixed-lineage thymic lymphomas may also result from primary defects of a natural T/myeloid lineage choice. ..
- Basal Ig Signaling and Receptor EditingMichael Farrar; Fiscal Year: 2009..abstract_text> ..
- Factors that modulate thymic outputThomas Serwold; Fiscal Year: 2006..In addition, it will be directly relevant to therapies that would involve skewing of T cell development to favor T cells with desired specificities. ..
- ANALYSIS OF THE MURINE ANTIBODY REPERTOIREGarnett Kelsoe; Fiscal Year: 2003..These immature cells proliferate and express the RAG2 recombinase protein but not BCL-6, a transcriptional repressor thought to be absolutely required for the GC ..
- GATA-3 in precursor commitment to the T lineageELLEN ROTHENBERG; Fiscal Year: 2003..Definition of mechanistic requirements for GATA-3 perturbation of T-cell development 3. Attempted rescue of GATA-3 overexpression effects by cotransduction with targets of specific repression. ..
- Application for a Fluorescence-Activated Cell SorterELLEN ROTHENBERG; Fiscal Year: 2003..This application is to replace the old sorter with a new sorter that will improve service to existing clients and permit the Facility to carry out new flow cytometric applications that have not been available to the user group before. ..
- GATA-3 in precursor commitment to the T lineageELLEN ROTHENBERG; Fiscal Year: 2006..Definition of mechanistic requirements for GATA-3 perturbation of T-cell development 3. Attempted rescue of GATA-3 overexpression effects by cotransduction with targets of specific repression. ..
- B Cell Expansion After Dendritic Cell ImmunizationMichael Jordan; Fiscal Year: 2004..My near term career path will involve ongoing basic research and study in order to improve my ultimate scientific productivity. ..
- LINEAGE COMMITMENT MECHANISMS IN LYMPHOID PRECURSORSELLEN ROTHENBERG; Fiscal Year: 2005..1 itself. ..