David Nemazee, PhD

Department of Immunology and Microbiology
California Campus

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.


Ph.D. (Cellular and Developmental Biology), Harvard University, 1983
B.A. (Biochemistry), Harvard University, Harvard College, 1979

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
1998-2017 Professor, Immunology and Microbial Science (IMS), Scripps Research
1983-1989 Scientific Member, Basel Institute for Immunology

Selected References

All Publications

Jardine JG, Ota T, Sok D, Pauthner M, Kulp DW, Kalyuzhniy O, Skog PD, Thinnes TC, Bhullar D, Briney B, Menis S, Jones M, Kubitz M, Spencer S, Adachi Y, Burton DR, Schief WR, Nemazee D. 2015. Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen. Science. Jun 18. pii: aac5894. [Epub ahead of print]

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