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David Nemazee, Ph.D.

Professor
Department of Immunology and Microbial Science
California Campus
Laboratory Website
nemazee@scripps.edu
(858) 784-9529

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

Receptor Editing In B Lymphocytes

The immune system eliminates lymphocytes with antigen receptors reactive to self-tissue and promotes the proliferation of cells that respond to foreign substances. We have discovered that one way that autoreactive lymphocytes are eliminated is not through cell death, but through an induced alteration of their antigen receptor genes. During their development in the bone marrow, immature B cells whose receptors bind antigens renew rearrangement of the genes for antibody light chains, allowing the cells to alter their antigen receptors and to lose self-reactivity. This process, called "receptor editing", is apparently controlled at the level of recombinase genes (RAGs). Recombinase genes can also become reactivated during the immune response to foreign antigens. We are currently trying to understand how signals from the antigen receptor can control recombinase and how this regulation is rewired at different stages of development.

Education

Ph.D., Harvard University, 1983

Professional Experience

B.A. Biochemistry, cum laude Harvard College, 1979
Ph.D. Cellular and Developmental Biology, Harvard University 1983
Scientific Member, Basel Institute for Immunology, Basel, Switzerland 1983-89 Immunology

Selected References

Ota, T., C. Doyle-Cooper, A. B. Cooper, K. J. Doores, M. Aoki-Ota, K. Le, W. R. Schief, R. T. Wyatt, D. R. Burton, and D. Nemazee. 2013. B Cells from Knock-in Mice Expressing Broadly Neutralizing HIV Antibody b12 Carry an Innocuous B Cell Receptor Responsive to HIV Vaccine Candidates. J Immunol 191:3179-3185. PMC3773231

Doyle-Cooper, C., K. E. Hudson, A. B. Cooper, T. Ota, P. Skog, P. E. Dawson, M. B. Zwick, W. R. Schief, D. R. Burton, and D. Nemazee. 2013. Immune Tolerance Negatively Regulates B Cells in Knock-In Mice Expressing Broadly Neutralizing HIV Antibody 4E10. J Immunol 191:3186-3191. PMC3773228

Duong, B. H., T. Ota, M. Aoki-Ota, A. B. Cooper, D. Ait-Azzouzene, J. L. Vela, A. L. Gavin, and D. Nemazee. 2011. Negative selection by IgM superantigen defines a B cell central tolerance compartment and reveals mutations allowing escape. J Immunol 187:5596-5605. PMC3227399

Hertz M., Kouskoff, V., Nakamura, T., and Nemazee, D. (1998). V (D)J recombinase induction in splenic B cells is inhibited by antigen receptor ligation. Nature, 394, 292-295.

Melamed, D., Benschop, R.J., Cambier, J.C., and Nemazee, D. (1998). Developmental regulation of B lymphocyte immune tolerance compartmentalizes clonal selection from receptor selection. Cell, 92, 173-182.

Hertz, M. and Nemazee, D. (1997). BCR ligation induces receptor editing in lgM+D- bone marrow B-cells in vitro. Immunity 6, 429-436.

Russell, D.M., Dembic, Z., Morahan, G., Miller JFAP, Bürki, K. and Nemazee, D. (1991) Peripheral deletion of self-reactive B-cells. Nature 354, 308-311