DAVID A NEMAZEE

Summary

Affiliation: The Scripps Research Institute
Country: USA

Publications

  1. pmc Decoration of T-independent antigen with ligands for CD22 and Siglec-G can suppress immunity and induce B cell tolerance in vivo
    Bao Hoa Duong
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Exp Med 207:173-87. 2010
  2. pmc An immunoglobulin C kappa-reactive single chain antibody fusion protein induces tolerance through receptor editing in a normal polyclonal immune system
    Djemel Ait-Azzouzene
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Exp Med 201:817-28. 2005
  3. pmc Liver-expressed Igkappa superantigen induces tolerance of polyclonal B cells by clonal deletion not kappa to lambda receptor editing
    Takayuki Ota
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Exp Med 208:617-29. 2011
  4. pmc B lymphocyte stimulator (BLyS) isoforms in systemic lupus erythematosus: disease activity correlates better with blood leukocyte BLyS mRNA levels than with plasma BLyS protein levels
    Christopher E Collins
    Division of Rheumatology, Department of Medicine, Los Angeles County University of Southern California Medical Center, Los Angeles, CA 90033, USA
    Arthritis Res Ther 8:R6. 2006
  5. ncbi request reprint Receptor editing in lymphocyte development and central tolerance
    David Nemazee
    Department of Immunology, The Scripps Research Institute, Mail Drop IMM 29, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Immunol 6:728-40. 2006
  6. pmc Receptor selection in B and T lymphocytes
    D Nemazee
    Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA
    Annu Rev Immunol 18:19-51. 2000
  7. ncbi request reprint Haplotype exclusion and receptor editing: irreconcilable differences?
    David Nemazee
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Semin Immunol 14:191-8; discussion 222-4. 2002
  8. ncbi request reprint Do B cells take advantage of 'missing self' recognition?
    David Nemazee
    Department of Immunology, Scripps Research Institute, La Jolla, Calif, USA
    Curr Dir Autoimmun 6:245-64. 2003
  9. ncbi request reprint Antigen receptor selection by editing or downregulation of V(D)J recombination
    David Nemazee
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, Mail Drop IM 29, La Jolla, CA 92037, USA
    Curr Opin Immunol 15:182-9. 2003
  10. ncbi request reprint Role of B cell antigen receptor in regulation of V(D)J recombination and cell survival
    D Nemazee
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Immunol Res 21:259-63. 2000

Research Grants

Collaborators

Detail Information

Publications31

  1. pmc Decoration of T-independent antigen with ligands for CD22 and Siglec-G can suppress immunity and induce B cell tolerance in vivo
    Bao Hoa Duong
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Exp Med 207:173-87. 2010
    ..The results suggest use of siglec ligand antigen constructs as an approach for inducing tolerance...
  2. pmc An immunoglobulin C kappa-reactive single chain antibody fusion protein induces tolerance through receptor editing in a normal polyclonal immune system
    Djemel Ait-Azzouzene
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Exp Med 201:817-28. 2005
    ..We also demonstrate the unique advantages of our model in the genetic and cellular analysis of immune tolerance...
  3. pmc Liver-expressed Igkappa superantigen induces tolerance of polyclonal B cells by clonal deletion not kappa to lambda receptor editing
    Takayuki Ota
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Exp Med 208:617-29. 2011
    ..The results suggest that deletion, not editing, is the major irreversible pathway of tolerance induction among peripheral B cells...
  4. pmc B lymphocyte stimulator (BLyS) isoforms in systemic lupus erythematosus: disease activity correlates better with blood leukocyte BLyS mRNA levels than with plasma BLyS protein levels
    Christopher E Collins
    Division of Rheumatology, Department of Medicine, Los Angeles County University of Southern California Medical Center, Los Angeles, CA 90033, USA
    Arthritis Res Ther 8:R6. 2006
    ..BLyS mRNA levels may be a helpful biomarker in the clinical monitoring of SLE patients...
  5. ncbi request reprint Receptor editing in lymphocyte development and central tolerance
    David Nemazee
    Department of Immunology, The Scripps Research Institute, Mail Drop IMM 29, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Immunol 6:728-40. 2006
    ....
  6. pmc Receptor selection in B and T lymphocytes
    D Nemazee
    Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA
    Annu Rev Immunol 18:19-51. 2000
    ..New information about receptor editing in T cells and B-1 B cells is also discussed...
  7. ncbi request reprint Haplotype exclusion and receptor editing: irreconcilable differences?
    David Nemazee
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Semin Immunol 14:191-8; discussion 222-4. 2002
    ..Thus, the immune system achieves both receptor selection and clonal selection, despite their partly antagonistic mechanisms...
  8. ncbi request reprint Do B cells take advantage of 'missing self' recognition?
    David Nemazee
    Department of Immunology, Scripps Research Institute, La Jolla, Calif, USA
    Curr Dir Autoimmun 6:245-64. 2003
  9. ncbi request reprint Antigen receptor selection by editing or downregulation of V(D)J recombination
    David Nemazee
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, Mail Drop IM 29, La Jolla, CA 92037, USA
    Curr Opin Immunol 15:182-9. 2003
    ..Many studies suggest that editing plays a central role in B and T lymphocyte repertoire development. Important recent evidence has been uncovered addressing the role of tolerance-induced editing in thymocytes...
  10. ncbi request reprint Role of B cell antigen receptor in regulation of V(D)J recombination and cell survival
    D Nemazee
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Immunol Res 21:259-63. 2000
    ..This process appears to be developmentally regulated, because it is confined to cells at an immature stage of development. Cells at later stages of development can be tolerized by apoptosis, but probably not by receptor editing...
  11. ncbi request reprint deltaBAFF, a splice isoform of BAFF, opposes full-length BAFF activity in vivo in transgenic mouse models
    Amanda L Gavin
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 175:319-28. 2005
    ..In contrast, BAFF transgenic mice had extraordinarily elevated Ig levels and increases in subsets of B cells. Unexpectedly, both BAFF and DeltaBAFF appeared to modulate the numbers of B-1 phenotype B cells...
  12. pmc Peripheral B cell tolerance and function in transgenic mice expressing an IgD superantigen
    Bao Hoa Duong
    Department of Immunology and Microbial Science, Kellogg School of Science and Technology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 184:4143-58. 2010
    ..This model should facilitate studies of peripheral B cell tolerance, with the advantages of allowing analysis of polyclonal populations, and of B cells naturally lacking IgD...
  13. pmc Regulation of the B cell receptor repertoire and self-reactivity by BAFF
    Miyo Ota
    Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 185:4128-36. 2010
    ..The results have positive implications for the clinical use of BAFF-depleting therapy...
  14. pmc Deletion of IgG-switched autoreactive B cells and defects in Fas(lpr) lupus mice
    Djemel Ait-Azzouzene
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 185:1015-27. 2010
    ....
  15. pmc Rearrangement of mouse immunoglobulin kappa deleting element recombining sequence promotes immune tolerance and lambda B cell production
    JOSE LUIS VELA
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Immunity 28:161-70. 2008
    ..These results provide insight into the mechanism of L chain isotype exclusion and indicate that RS has a physiological role in promoting the formation of lambda L chain-expressing B cells...
  16. pmc Basal B cell receptor-directed phosphatidylinositol 3-kinase signaling turns off RAGs and promotes B cell-positive selection
    Laurent Verkoczy
    Department of Immunology, Kellogg School of Science and Technology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 178:6332-41. 2007
    ..Taken together, our results provide evidence that PI3K signaling is an important cue required for fostering development of B cells carrying a useful BCR...
  17. pmc Adjuvant-enhanced antibody responses in the absence of toll-like receptor signaling
    Amanda L Gavin
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037 USA
    Science 314:1936-8. 2006
    ..This may have important implications in the use and development of vaccine adjuvants...
  18. ncbi request reprint Effect of cell:cell competition and BAFF expression on peripheral B cell tolerance and B-1 cell survival in transgenic mice expressing a low level of Igkappa-reactive macroself antigen
    Djemel Ait-Azzouzene
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Eur J Immunol 36:985-96. 2006
    ....
  19. ncbi request reprint Paucity of V-D-D-J rearrangements and VH replacement events in lupus prone and nonautoimmune TdT-/- and TdT+/+ mice
    Lisa C Watson
    The Scripps Research Institute, Department of Immunology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Immunol 177:1120-8. 2006
    ....
  20. ncbi request reprint Split tolerance in peripheral B cell subsets in mice expressing a low level of Igkappa-reactive ligand
    Djemel Ait-Azzouzene
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 176:939-48. 2006
    ..These findings suggest distinct signaling thresholds for tolerance among peripheral B cell subsets reactive with an identical ligand...
  21. pmc Receptor editing and marginal zone B cell development are regulated by the helix-loop-helix protein, E2A
    Melanie W Quong
    Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA
    J Exp Med 199:1101-12. 2004
    ..Additionally, we propose a model in which E-proteins enforce the developmental checkpoint at the immature B cell stage...
  22. pmc DeltaBAFF, an alternate splice isoform that regulates receptor binding and biopresentation of the B cell survival cytokine, BAFF
    Amanda L Gavin
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 278:38220-8. 2003
    ..Thus, alternative splicing of the BAFF gene suppresses BAFF B cell stimulatory function in several ways, and deltaBAFF may promote other functions as well...
  23. pmc Reduced receptor editing in lupus-prone MRL/lpr mice
    Jennifer L Lamoureux
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Exp Med 204:2853-64. 2007
    ..Less efficient receptor editing could allow some autoreactive cells to escape from the bone marrow in lupus-prone mice, thus predisposing to autoimmunity...
  24. ncbi request reprint Peripheral B lymphocyte tolerance
    Amanda Gavin
    Department of Immunology, and Macromolecular Structure and Chemistry Program, The Scripps Research Institute, La Jolla, CA 92037, USA
    Keio J Med 53:151-8. 2004
    ..Preliminary studies from transgenic mice overexpressing wild type or DBAFF are consistent with a possible regulatory role for DBAFF, raising the possibility that the relative expression levels of BAFF and DBAFF regulates tolerance...
  25. pmc Suppression of IgE B cells and IgE binding to Fc(epsilon)RI by gene therapy with single-chain anti-IgE
    Takayuki Ota
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 182:8110-7. 2009
    ..These studies have important implications for the optimal design of safe and effective anti-IgE therapies and suggest that the IgE memory B cells may be targeted by such genetic Ab therapies...
  26. ncbi request reprint The scope of receptor editing and its association with autoimmunity
    Laurent K Verkoczy
    Department of Immunology, The Scripps Research Institute, Mail Drop IMM 29, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Curr Opin Immunol 16:808-14. 2004
    ..New data suggest that editing can efficiently eliminate autoreactivity, yet, in an autoimmune context, secondary antibody gene rearrangements might also contribute to autoimmunity...
  27. pmc A mutation of Ikbkg causes immune deficiency without impairing degradation of IkappaB alpha
    Owen M Siggs
    Department of Genetics, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 107:3046-51. 2010
    ..This selective loss of function highlights the immunological importance of NEMO-regulated pathways beyond IkappaB alpha degradation, and offers a biochemical explanation for rare immune deficiencies in man...
  28. pmc Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci
    Kristina Beck
    Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA
    J Exp Med 206:2271-84. 2009
    ..We propose that in the pre-B and immature B cell compartments, gradients of E12 and E47 activities are established to mechanistically regulate the sequential rearrangement of the Ig light chain genes...
  29. ncbi request reprint Tolerance-induced receptor selection: scope, sensitivity, locus specificity, and relationship to lymphocyte-positive selection
    Djemel Ait-Azzouzene
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Immunol Rev 197:219-30. 2004
    ..The present review highlights the contributions from our laboratory over several years to elucidate these features...
  30. pmc FGD2, a CDC42-specific exchange factor expressed by antigen-presenting cells, localizes to early endosomes and active membrane ruffles
    Christoph Huber
    Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 283:34002-12. 2008
    ..These findings are consistent with a role of FGD2 in leukocyte signaling and vesicle trafficking in cells specialized to present antigen in the immune system...
  31. pmc A role for nuclear factor kappa B/rel transcription factors in the regulation of the recombinase activator genes
    Laurent Verkoczy
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    Immunity 22:519-31. 2005
    ..Rapidly activated NF kappa B pathways may facilitate prompt antigen receptor-regulated changes in RAG expression important for editing and haplotype exclusion...

Research Grants6

  1. RECEPTOR EDITING IN B CELLS
    David Nemazee; Fiscal Year: 2010
    ..ARRA Response:2 R01 A1033608-16A1 ARRA Response: 2 ROl A1033608-16A1 F-- protein GSK3$3 is poorly activated by BCR signaling in immature B cells. L-' ..
  2. Immune Tolerance in Non-clonal Immune Systems
    David Nemazee; Fiscal Year: 2003
    ..These studies should have broad applications to questions of lymphocyte activation, differentiation, and survival. ..
  3. Assessment of BAFF as a mucosal HIV DNA vaccine adjuvant
    David Nemazee; Fiscal Year: 2005
    ....
  4. Manipulating the IgE response with IgE-reactive macroself antigen
    David Nemazee; Fiscal Year: 2007
    ..Furthermore, IgE macroself Ag-mediated suppression by gene transfer will be assessed both during and after antigenic sensitization. [unreadable] [unreadable]..
  5. B LYMPHOCYTE TOLERANCE IN HEALTH AND AUTOIMMUNITY
    David Nemazee; Fiscal Year: 2009
    ....
  6. Effect of BAFF on threshold of B cell tolerance
    David Nemazee; Fiscal Year: 2010
    ..The long-term goal of these studies is to understand how BAFF promotes Sjogren's Syndrome and to determine the basic parameters regulating immune tolerance. ..