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Nemazee, David
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Nemazee, David

Faculty Member
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Positions

  • 2017 - Professor, Immunology and Microbiology , Scripps Research
  • 1998 - Faculty Member, Skaggs Graduate School of Chemical and Biological Sciences , Scripps Research
  • 1998 - 2017 Professor, Immunology and Microbial Science (IMS) , Scripps Research
  • 1983 - 1989 Scientific Member, Basel Institute for Immunology
Dr. David Nemazee studies "receptor editing," a novel immunological tolerance mechanism in which developing B lymphocytes that carry autoreactive cell surface antibody are stimulated to "reprogram" their immunoglobulin genes by further rounds of DNA recombination.

Contact

  • nemazee@scripps.edu

Websites

  • David Nemazee, Ph.D.
  • Laboratory Website
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Publications

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  • 59

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    • Wec, A. Z., Wrapp, D., Herbert, A. S., Maurer, D. P., Haslwanter, D., Sakharkar, M., Jangra, R. K., Dieterle, M. E., Lilov, A., Huang, D. L., Tse, L. V., Johnson, N. V., et al. Broad neutralization of SARS-related viruses by human monoclonal antibodies Science  2020 369:731-736  DOI:10.1126/science.abc7424  PMID:32540900  PMCID:PMC7299279
    • Xiao, C. C., Nemazee, D., Gonzalez-Martin, A. MicroRNA control of B cell tolerance, autoimmunity and cancer Seminars in Cancer Biology  2020 64:102-107  DOI:10.1016/j.semcancer.2019.04.004  PMID:32522353  PMCID:PMC7295097
    • Phillips, N., Ke, E., Nham, A., Seidl, M., Freeman, B., Abadejos, J. R., Xiao, C., Nemazee, D., Ku, M. C., Kirak, O. Prediabetes Induced by a Single Autoimmune B Cell Clone Frontiers in Immunology  2020 11  DOI:10.3389/fimmu.2020.01073  PMID:32625203  PMCID:PMC7314986
    • Grodeland, G., Baranowska-Hustad, M., Abadejos, J., Blane, T. R., Teijaro, J., Nemazee, D., Bogen, B. Induction of cross-reactive and protective antibody responses after DNA vaccination with MHCII-targeted stem domain from influenza hemagglutinin Frontiers in Immunology  2020 11  DOI:10.3389/fimmu.2020.00431  PMID:32269566  PMCID:PMC7112135
    • Huang, D. L., Abbott, R. K., Havenar-Daughton, C., Skog, P. D., Al-Kolla, R., Groschel, B., Blane, T. R., Menis, S., Tran, J. T., Thinnes, T. C., Volpi, S. A., Liguori, A., et al. B cells expressing authentic naive human VRC01-class BCRs can be recruited to germinal centers and affinity mature in multiple independent mouse models Proceedings of the National Academy of Sciences of the United States of America  2020 117:22920-22931  DOI:10.1073/pnas.2004489117  PMID:32873644  PMCID:PMC7502816
    • Rogers, T. F., Zhao, F., Huang, D. L., Beutler, N., Burns, A., He, W. T., Limbo, O., Smith, C., Song, G., Woehl, J., Yang, L. L., Abbott, R. K., et al. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model Science  2020 369:956-963  DOI:10.1126/science.abc7520  PMID:32540903  PMCID:PMC7299280
    • Antanasijevic, A., Ueda, G., Brouwer, P. J. M., Copps, J., Huang, D. L., Allen, J. D., Cottrell, C. A., Yasmeen, A., Sewall, L. M., Bontjer, I., Ketas, T. J., Turner, H. L., et al. Structural and functional evaluation ofde novo-designed, two-component nanoparticle carriers for HIV Env trimer immunogens PLoS Pathogens  2020 16  DOI:10.1371/journal.ppat.1008665  PMID:32780770  PMCID:PMC7418955
    • Melo, M., Porter, E., Zhang, Y., Silva, M., Li, N., Dobosh, B., Liguori, A., Skog, P., Landais, E., Menis, S., Sok, D., Nemazee, D., et al. Immunogenicity of RNA replicons encoding HIV Env immunogens designed for self-assembly into nanoparticles Molecular Therapy  2019 27:2080-2090  DOI:10.1016/j.ymthe.2019.08.007  PMID:31515132  PMCID:PMC6904793
    • Bancroft, T., DeBuysscher, B. L., Weidle, C., Schwartz, A., Wall, A., Gray, M. D., Feng, J., Steach, H. R., Fitzpatrick, K. S., Gewe, M. M., Skog, P. D., Doyle-Cooper, C., et al. Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes Journal of Experimental Medicine  2019 216:2331-2347  DOI:10.1084/jem.20190164  PMID:31345930  PMCID:PMC6780997
    • Sinha, R. K., Flynn, R., Zaiken, M., Paz, K., Gavin, A. L., Nemazee, D., Fernandez, J. A., Xu, X., Griffin, J. H., Blazar, B. R. Activated protein C ameliorates chronic graft-versus-host disease by PAR1-dependent biased cell signaling on T cells Blood  2019 134:776-781  DOI:10.1182/blood.2019001259  PMID:31243040  PMCID:PMC6716074
    • Voss, J. E., Gonzalez-Martin, A., Andrabi, R., Fuller, R. P., Murrell, B., McCoy, L. E., Porter, K., Huang, D., Li, W., Sok, D., Le, K., Briney, B., et al. Reprogramming the antigen specificity of B cells using genome-editing technologies Elife  2019 8  DOI:10.7554/eLife.42995  PMID:30648968  PMCID:PMC6355199
    • He, L., Kumar, S., Allen, J. D., Huang, D. L., Lin, X., Mann, C. J., Saye-Francisco, K. L., Copps, J., Sarkar, A., Blizard, G. S., Ozorowski, G., Sok, D., et al. HIV-1 vaccine design through minimizing envelope metastability Science Advances  2018 4  DOI:10.1126/sciadv.aau6769  PMID:30474059  PMCID:PMC6248932
    • Gavin, A. L., Huang, D., Huber, C., Martensson, A., Tardif, V., Skog, P. D., Blane, T. R., Thinnes, T. C., Osborn, K., Chong, H. S., Kargaran, F., Kimm, P., et al. PLD3 and PLD4 are single-stranded acid exonucleases that regulate endosomal nucleic-acid sensing Nature Immunology  2018 19:942-953  DOI:10.1038/s41590-018-0179-y  PMID:30111894  PMCID:PMC6105523
    • Kolenbrander, A., Grewe, B., Nemazee, D., Uberla, K., Temchura, V. Generation of T follicular helper cells in vitro: requirement for B-cell receptor cross-linking and cognate B- and T-cell interaction Immunology  2018 153:214-224  DOI:10.1111/imm.12834  PMID:28881401  PMCID:PMC5765376
    • Abbott, R. K., Lee, J. H., Menis, S., Skog, P., Rossi, M., Ota, T., Kulp, D. W., Bhullar, D., Kalyuzhniy, O., Havenar-Daughton, C., Schief, W. R., Nemazee, D., et al. Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens Immunity  2018 48:133-146  DOI:10.1016/j.immuni.2017.11.023  PMID:29287996  PMCID:PMC5773359
    • Medina-Ramirez, M., Garces, F., Escolano, A., Skog, P., de Taeye, S. W., Del Moral-Sanchez, I., McGuire, A. T., Yasmeen, A., Behrens, A. J., Ozorowski, G., van den Kerkhof, Tlgm, Freund, N. T., et al. Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo Journal of Experimental Medicine  2017 214:2573-2590  DOI:10.1084/jem.20161160  PMID:28847869  PMCID:PMC5584115
    • Martinic, M. M., Caminschi, I., O'Keeffe, M., Thinnes, T. C., Grumont, R., Gerondakis, S., McKay, D. B., Nemazee, D., Gavin, A. L. The bacterial peptidoglycan-sensing molecules NOD1 and NOD2 promote CD8+ thymocyte selection Journal of Immunology  2017 198:2649-2660  DOI:10.4049/jimmunol.1601462  PMID:28202617  PMCID:PMC5360474
    • Briney, B., Sok, D., Jardine, J. G., Kulp, D. W., Skog, P., Menis, S., Jacak, R., Kalyuzhniy, O., de Val, N., Sesterhenn, F., Le, K. M., Ramos, A., et al. Tailored immunogens direct affinity maturation toward HIV neutralizing antibodies Cell  2016 166:1459-1470  DOI:10.1016/j.cell.2016.08.005  PMID:27610570  PMCID:PMC5018249
    • Lai, M., Gonzalez-Martin, A., Cooper, A. B., Oda, H., Jin, H. Y., Shepherd, J., He, L., Zhu, J., Nemazee, D., Xiao, C. Regulation of B-cell development and tolerance by different members of the miR-17∼92 family microRNAs Nature Communications  2016 7  DOI:10.1038/ncomms12207  PMID:27481093  PMCID:PMC4974641
    • He, L., de Val, N., Morris, C. D., Vora, N., Thinnes, T. C., Kong, L., Azadnia, P., Sok, D., Zhou, B., Burton, D. R., Wilson, I. A., Nemazee, D., et al. Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles Nature Communications  2016 7  DOI:10.1038/ncomms12041  PMID:27349934  PMCID:PMC4931238
    • Ingale, J., Stano, A., Guenaga, J., Sharma, S. K., Nemazee, D., Zwick, M. B., Wyatt, R. T. High-density array of well-ordered HIV-1 spikes on synthetic liposomal nanoparticles efficiently activate B cells Cell Reports  2016 15:1986-1999  DOI:10.1016/j.celrep.2016.04.078  PMID:27210756  PMCID:PMC4889521
    • Gonzalez-Martin, A., Adams, B. D., Lai, M., Shepherd, J., Salvador-Bernaldez, M., Salvador, J. M., Lu, J., Nemazee, D., Xiao, C. The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity Nature Immunology  2016 17:433-440  DOI:10.1038/ni.3385  PMID:26901150  PMCID:PMC4803625
    • Lang, J., Ota, T., Kelly, M., Strauch, P., Freed, B. M., Torres, R. M., Nemazee, D., Pelanda, R. Receptor editing and genetic variability in human autoreactive B cells Journal of Experimental Medicine  2016 213:93  DOI:10.1084/jem.20151039  PMID:26694971  PMCID:PMC4710202
    • Jardine, J. G., Ota, T., Sok, D., Pauthner, M., Kulp, D. W., Kalyuzhniy, O., Skog, P. D., Thinnes, T. C., Bhullar, D., Briney, B., Menis, S., Jones, M., et al. Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen Science  2015 349:156-161  DOI:10.1126/science.aac5894  PMID:26089355  PMCID:PMC4669217
    • Ota, T., Doyle-Cooper, C., Cooper, A. B., Doores, K. J., Aoki-Ota, M., Le, K., Schief, W. R., Wyatt, R. T., Burton, D. R., Nemazee, D. B cells from knock-in mice expressing broadly neutralizing HIV antibody b12 carry an innocuous B cell receptor responsive to HIV vaccine candidates Journal of Immunology  2013 191:3179-3185  DOI:10.4049/jimmunol.1301283  PMID:23940273  PMCID:PMC3773231
    • Doyle-Cooper, C., Hudson, K. E., Cooper, A. B., Ota, T., Skog, P., Dawson, P. E., Zwick, M. B., Schief, W. R., Burton, D. R., Nemazee, D. Immune tolerance negatively regulates B cells in knock-in mice expressing broadly neutralizing HIV antibody 4E10 Journal of Immunology  2013 191:3186-3191  DOI:10.4049/jimmunol.1301285  PMID:23940276  PMCID:PMC3773228
    • Jardine, J., Julien, J. P., Menis, S., Ota, T., Kalyuzhniy, O., McGuire, A., Sok, D., Huang, P. S., MacPherson, S., Jones, M., Nieusma, T., Mathison, J., et al. Rational HIV immunogen design to target specific germline B cell receptors Science  2013 340:711-716  DOI:10.1126/science.1234150  PMID:23539181  PMCID:PMC3689846
    • Doores, K. J., Huber, M., Le, K. M., Wang, S. K., Doyle-Cooper, C., Cooper, A., Pantophlet, R., Wong, C. H., Nemazee, D., Burton, D. R. 2G12-expressing B cell lines may aid in HIV carbohydrate vaccine design strategies Journal of Virology  2013 87:2234-2241  DOI:10.1128/jvi.02820-12  PMID:23221565  PMCID:PMC3571453
    • Ota, T., Doyle-Cooper, C., Cooper, A. B., Huber, M., Falkowska, E., Doores, K. J., Hangartner, L., Le, K., Sok, D., Jardine, J., Lifson, J., Wu, X. L., et al. Anti-HIV B Cell lines as candidate vaccine biosensors Journal of Immunology  2012 189:4816-4824  DOI:10.4049/jimmunol.1202165  PMID:23066156  PMCID:PMC3626558
    • Aoki-Ota, M., Torkamani, A., Ota, T., Schork, N., Nemazee, D. Skewed primary Igκ repertoire and V-J joining in C57BL/6 mice: implications for recombination accessibility and receptor editing Journal of Immunology  2012 188:2305-2315  DOI:10.4049/jimmunol.1103484  PMID:22287713  PMCID:PMC3288532
    • Duong, B. H., Ota, T., Aoki-Ota, M., Cooper, A. B., Ait-Azzouzene, D., Vela, J. L., Gavin, A. L., Nemazee, D. Negative selection by IgM superantigen defines a B cell central tolerance compartment and reveals mutations allowing escape Journal of Immunology  2011 187:5596-5605  DOI:10.4049/jimmunol.1102479  PMID:22043016  PMCID:PMC3227399
    • Siggs, O. M., Arnold, C. N., Huber, C., Pirie, E., Xia, Y., Lin, P., Nemazee, D., Beutler, B. The P4-type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrow Nature Immunology  2011 12:434-440  DOI:10.1038/ni.2012  PMID:21423172  PMCID:PMC3079768
    • Ota, T., Ota, M., Duong, B. H., Gavin, A. L., Nemazee, D. Liver-expressed Igκ superantigen induces tolerance of polyclonal B cells by clonal deletion not κ to λ receptor editing Journal of Experimental Medicine  2011 208:617-629  DOI:10.1084/jem.20102265  PMID:21357741  PMCID:PMC3058582
    • Ota, M., Duong, B. H., Torkamani, A., Doyle, C. M., Gavin, A. L., Ota, T., Nemazee, D. Regulation of the B cell receptor repertoire and self-reactivity by BAFF Journal of Immunology  2010 185:4128-4136  DOI:10.4049/jimmunol.1002176  PMID:20817867  PMCID:PMC3263398
    • Ait-Azzouzene, D., Kono, D. H., Gonzalez-Quintial, R., McHeyzer-Williams, L. J., Lim, M., Wickramarachchi, D., Gerdes, T., Gavin, A. L., Skog, P., McHeyzer-Williams, M. G., Nemazee, D., Theofilopoulos, A. N. Deletion of IgG-switched autoreactive B cells and defects in Fas(lpr) lupus mice Journal of Immunology  2010 185:1015-1027  DOI:10.4049/jimmunol.1000698  PMID:20554953  PMCID:PMC3641794
    • Duong, B. H., Ota, T., Ait-Azzouzene, D., Aoki-Ota, M., Vela, J. L., Huber, C., Walsh, K., Gavin, A. L., Nemazee, D. Peripheral B cell tolerance and function in transgenic mice expressing an IgD superantigen Journal of Immunology  2010 184:4143-4158  DOI:10.4049/jimmunol.0903564  PMID:20231687  PMCID:PMC2874719
    • Siggs, O. M., Berger, M., Krebs, P., Arnold, C. N., Eidenschenk, C., Huber, C., Pirie, E., Smart, N. G., Khovananth, K., Xia, Y., McInerney, G., Hedestam, G. B. K., et al. A mutation of Ikbkg causes immune deficiency without impairing degradation of IκBα Proceedings of the National Academy of Sciences of the United States of America  2010 107:3046-3051  DOI:10.1073/pnas.0915098107  PMID:20133626  PMCID:PMC2840324
    • Duong, B. H., Tian, H., Ota, T., Completo, G., Han, S. F., Vela, J. L., Ota, M., Kubitz, M., Bovin, N., Paulson, J., Nemazee, D. Decoration of T-independent antigen with ligands for CD22 and Siglec-G can suppress immunity and induce B cell tolerance in vivo Journal of Experimental Medicine  2010 207:173-187  DOI:10.1084/jem.20091873  PMID:20038598  PMCID:PMC2812539
    • Beck, K., Peak, M. M., Ota, T., Nemazee, D., Murre, C. Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci Journal of Experimental Medicine  2009 206:2271-2284  DOI:10.1084/jem.20090756  PMID:19752184  PMCID:PMC2757879
    • Ota, T., Aoki-Ota, M., Duong, B. H., Nemazee, D. Suppression of IgE B cells and IgE binding to Fc(epsilon)RI by gene therapy with single-chain anti-IgE Journal of Immunology  2009 182:8110-8117  DOI:10.4049/jimmunol.0900300  PMID:19494337  PMCID:PMC2874974
    • Huber, C., Martensson, A., Bokoch, G. M., Nemazee, D., Gavin, A. L. FGD2, a CDC42-specific exchange factor expressed by antigen-presenting cells, localizes to early endosomes and active membrane ruffles Journal of Biological Chemistry  2008 283:34002-34012  DOI:10.1074/jbc.M803957200  PMID:18838382  PMCID:PMC2590680
    • Vela, J. L., Aft-Azzouzene, D., Duong, B. H., Ota, T., Nemazee, D. Rearrangement of mouse immunoglobulin kappa deleting element recombining sequence promotes immune tolerance and lambda B cell production Immunity  2008 28:161-170  DOI:10.1016/j.immuni.2007.12.011  PMID:18261939  PMCID:PMC2351955
    • Lamoureux, J. L., Watson, L. C., Cherrier, M., Skog, P., Nemazee, D., Feeney, A. J. Reduced receptor editing in lupus-prone MRL/1pr mice Journal of Experimental Medicine  2007 204:2853-2864  DOI:10.1084/jem.20071268  PMID:17967905  PMCID:PMC2118512
    • Wucherpfennig, K. W., Allen, P. M., Celada, F., Cohen, I. R., De Boer, R., Garcia, K. C., Goldstein, B., Greenspan, R., Hafler, D., Hodgkin, P., Huseby, E. S., Krakauer, D. C., et al. Polyspecificity of t cell and b cell receptor recognition Seminars in Immunology  2007 19:216-224  DOI:10.1016/j.simm.2007.02.012  PMID:17398114
    • Verkoczy, L., Duong, B., Skog, P., Ait-Azzouzene, D., Puri, K., Vela, J. L., Nemazee, D. Basal B cell receptor-directed phosphatidylinositol 3-kinase signaling turns off rags and promotes B cell-positive selection Journal of Immunology  2007 178:6332-6341  PMID:17475862  PMCID:PMC3777394
    • Vela, J. L., Nemazee, D. Role of RS/κDE in B cell receptor editing Advances in Experimental Medicine and Biology  2007 596:169-172  DOI:10.1007/0-387-46530-8_16  PMID:17338186
    • Gavin, A. L., Hoebe, K., Duong, B., Ota, T., Martin, C., Beutler, B., Nemazee, D. Adjuvant-enhanced antibody responses in the absence of toll-like receptor signaling Science  2006 314:1936-1938  DOI:10.1126/science.1135299  PMID:17185603  PMCID:PMC1868398
    • Nemazee, D. Receptor editing in lymphocyte development and central tolerance Nature Reviews Immunology  2006 6:728-740  DOI:10.1038/nri1939  PMID:16998507
    • Watson, L. C., Moffatt-Blue, C. S., McDonald, R. Z., Kompfner, E., Ait-Azzouzene, D., Nemazee, D., Theofilopoulos, A. N., Kono, D. H., Feeney, A. J. Paucity of V-D-D-J rearrangements and V-H replacement events in lupus prone and nonautoimmune TdT(-/-) and TdT(+/+) mice Journal of Immunology  2006 177:1120-1128  PMID:16818769
    • Nemazee, D., Gavin, A., Hoebe, K., Beutler, B. Immunology: Toll-like receptors and antibody responses Nature  2006 441:E4  DOI:10.1038/nature04875  PMID:16710369  PMCID:PMC3787862
    • Ait-Azzouzene, D., Gavin, A. L., Skog, P., Duong, B., Nemazee, D. 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 IgK-reactive macroself antigen European Journal of Immunology  2006 36:985-996  DOI:10.1002/eji.2005355811  PMID:16511898
    • Ait-Azzouzene, D., Verkoczy, L., Duong, B., Skog, P., Gavin, A. L., Nemazee, D. Split tolerance in peripheral B cell subsets in mice expressing a low level of Ig kappa-reactive ligand Journal of Immunology  2006 176:939-948  PMID:16393979
    • Collins, C. E., Gavin, A. L., Migone, T. S., Hilbert, D. M., Nemazee, D., Stohl, W. 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 Arthritis Research & Therapy  2006 8:R6  DOI:10.1186/ar1855  PMID:16356193  PMCID:PMC1526545
    • Gavin, A. L., Duong, B., Skog, P., Ait-Azzouzene, D., Greaves, D. R., Scott, M. L., Nemazee, D. delta BAFF, a splice isoform of BAFF, opposes full-length BAFF activity in vivo in transgenic mouse models Journal of Immunology  2005 175:319-328  PMID:15972664
    • Peters, B., Sidney, J., Bourne, P., Bui, H. H., Buus, S., Doh, G., Fleri, W., Kronenberg, M., Kubo, R., Lund, O., Nemazee, D., Ponomarenko, J. V., et al. The design and implementation of the immune epitope database and analysis resource Immunogenetics  2005 57:326-336  DOI:10.1007/s00251-005-0803-5  PMID:15895191  PMCID:PMC4780685
    • Verkoczy, L., Ait-Azzouzene, D., Skog, P., Martensson, A., Lang, J., Duong, B., Nemazee, D. A role for nuclear factor kappa b/rel transcription factors in the regulation of the recombinase activator genes Immunity  2005 22:519-531  DOI:10.1016/j.immuni.2005.03.006  PMID:15845455  PMCID:PMC3792720
    • Ait-Azzouzene, D., Verkoczy, L., Peters, J., Gavin, A., Skog, P., Vela, J. L., Nemazee, D. An immunoglobulin Cκ-reactive single chain antibody fusion protein induces tolerance through receptor editing in a normal polyclonal immune system Journal of Experimental Medicine  2005 201:817-828  DOI:10.1084/jem.20041854  PMID:15738053  PMCID:PMC2212821
    • Verkoczy, L. K., Martensson, A. S., Nemazee, D. The scope of receptor editing and its association with autoimmunity Current Opinion in Immunology  2004 16:808-814  DOI:10.1016/j.coi.2004.09.017  PMID:15511677
    • Quong, M. W., Martensson, A., Langerak, A. W., Rivera, R. R., Nemazee, D., Murre, C. Receptor editing and marginal zone b cell development are regulated by the helix-loop-helix protein, e2a Journal of Experimental Medicine  2004 199:1101-1112  DOI:10.1084/jem.20031180  PMID:15078898  PMCID:PMC2211894
    • Nemazee, D., Serreze, D. V., Chapman, H. D., Dombrowsky, J., Silveira, P. A., Johnson, Ellis B cell selection defects underlie the development of diabetogenic apcs in nonobese diabetic mice Journal of Immunology  2004 172:5086-5094  PMID:15067092  PMCID:PMC3792717
    • Gavin, A., Ait-Azzouzene, D., Martensson, A., Duong, B., Verkoczy, L., Vela, J. L., Skog, P., Nemazee, D. Peripheral B lymphocyte tolerance Keio Journal of Medicine  2004 53:151-158  PMID:15477728
    • Ait-Azzouzene, D., Skog, P., Retter, M., Kouskoff, V., Hertz, M., Lang, J., Kench, J., Chumley, M., Melamed, D., Sudaria, J., Gavin, A., Martensson, A., et al. Tolerance-induced receptor selection: scope, sensitivity, locus specificity, and relationship to lymphocyte-positive selection Immunological Reviews  2004 197:219-230  DOI:10.1111/j.0105-2896.2004.0106.x  PMID:14962198
    • Gavin, A. L., Ait-Azzouzene, D., Ware, C. F., Nemazee, D. delta BAFF, an alternate splice isoform that regulates receptor binding and biopresentation of the B cell survival cytokine, BAFF Journal of Biological Chemistry  2003 278:38220-38228  DOI:10.1074/jbc.M306852200  PMID:12867412  PMCID:PMC3792716
    • Pape, K. A., Kouskoff, V., Nemazee, D., Tang, H. L., Cyster, J. G., Tze, L. E., Hippen, K. L., Behrens, T. W., Jenkins, M. K. Visualization of the genesis and fate of isotype-switched b cells during a primary immune response Journal of Experimental Medicine  2003 197:1677-1687  DOI:10.1084/jem.20012065  PMID:12796466  PMCID:PMC2193962
    • Nemazee, D., Hogquist, K. A. Antigen receptor selection by editing or downregulation of v(d)j recombination Current Opinion in Immunology  2003 15:182-189  DOI:10.1016/s0952-7915(03)00008-6  PMID:12633668
    • Nemazee, D., Martensson, A., Verkoczy, L. Haplotype exclusion and receptor editing: Irreconcilable differences? Seminars in Immunology  2002 14:191-198  DOI:10.1016/s1044-5323(02)00042-8  PMID:12160646
    • Kouskoff, V., Nemazee, D. Role of receptor editing and revision in shaping the b and t lymphocyte repertoire Life Sciences  2001 69:1105-1113  DOI:10.1016/s0024-3205(01)01219-x  PMID:11508343
    • Casellas, R., Shih, T. A. Y., Kleinewietfeld, M., Rakonjac, J., Nemazee, D., Rajewsky, K., Nussenzweig, M. C. Contribution of receptor editing to the antibody repertoire Science  2001 291:1541-1544  DOI:10.1126/science.1056600  PMID:11222858
    • Melamed, D., Miri, E., Leider, N., Nemazee, D. Unexpected autoantibody production in membrane ig-mu-deficient/lpr mice Journal of Immunology  2000 165:4353-4358  PMID:11035071
    • Buhl, A. M., Nemazee, D., Cambier, J. C., Rickert, R., Hertz, M. B-cell antigen receptor competence regulates b-lymphocyte selection and survival Immunological Reviews  2000 176:141-153  PMID:11043774
    • Kouskoff, V., Lacaud, G., Pape, K., Retter, M., Nemazee, D. B cell receptor expression level determines the fate of developing b lymphocytes: Receptor editing versus selection Proceedings of the National Academy of Sciences of the United States of America  2000 97:7435-7439  DOI:10.1073/pnas.130182597  PMID:10829082  PMCID:PMC16563
    • Chumley, M. J., Dal Porto, J. M., Kawaguchi, S., Cambier, J. C., Nemazee, D., Hardy, R. R. A v(h)11v(kappa)9b cell antigen receptor drives generation of cd5(+) b cells both in vivo and in vitro Journal of Immunology  2000 164:4586-4593  PMID:10779761
    • Kouskoff, V., Lacaud, G., Nemazee, D. T cell-independent rescue of b lymphocytes from peripheral immune tolerance Science  2000 287:2501-2503  DOI:10.1126/science.287.5462.2501  PMID:10741972
    • Lang, J., Nemazee, D. B cell clonal elimination induced by membrane-bound self-antigen may require repeated antigen encounter or cell competition European Journal of Immunology  2000 30:689-696  DOI:10.1002/1521-4141(200002)30:2<689::aid-immu689>3.3.co;2-9  PMID:10671228
    • Nemazee, D., Kouskoff, V., Hertz, M., Lang, J., Melamed, D., Pape, K., Retter, M. B-cell-receptor-dependent positive and negative selection in immature b cells Current Topics in Microbiology and Immunology  2000 245:57-71  PMID:10533318
    • Nemazee, D. Receptor selection in b and t lymphocytes Annual Review of Immunology  2000 18:19-51  DOI:10.1146/annurev.immunol.18.1.19  PMID:10837051  PMCID:PMC3822044
    • Nemazee, D. Role of b cell antigen receptor in regulation of v(d)j recombination and cell survival Immunologic Research  2000 21:259-263  DOI:10.1385/ir:21:2-3:259  PMID:10852126
    • Benschop, R. J., Melamed, D., Nemazee, D., Cambier, J. C. Distinct signal thresholds for the unique antigen receptor-linked gene expression programs in mature and immature b cells Journal of Experimental Medicine  1999 190:749-756  DOI:10.1084/jem.190.6.749  PMID:10499913
    • Kench, J. A., Russell, D. M., Fadok, V. A., Young, S. K., Worthen, G. S., Jones-Carson, J., Henson, J. E., Henson, P. M., Nemazee, D. Aberrant wound healing and tgf-beta production in the autoimmune-prone mrl/+ mouse Clinical Immunology  1999 92:300-310  DOI:10.1006/clim.1999.4754  PMID:10479535
    • Retter, M. V., Nemazee, D. Receptor editing: Genetic reprogramming of autoreactive lymphocytes Cell Biochemistry and Biophysics  1999 31:81-88  DOI:10.1007/bf02738156  PMID:10505669
    • Kouskoff, V., Famiglietti, S., Lacaud, G., Lang, P., Rider, J. E., Kay, B. K., Cambier, J. C., Nemazee, D. Antigens varying in affinity for the b cell receptor induce differential b lymphocyte responses Journal of Experimental Medicine  1998 188:1453-1464  DOI:10.1084/jem.188.8.1453  PMID:9782122
    • Retter, M. W., Nemazee, D. Receptor editing occurs frequently during normal b cell development Journal of Experimental Medicine  1998 188:1231-1238  DOI:10.1084/jem.188.7.1231  PMID:9763602
    • Ait-Azzouzene, D., Gendron, M. C., Houdayer, M., Langkopf, A., Burki, K., Nemazee, D., Kanellopoulos-Langevin, C. Maternal b lymphocytes specific for paternal histocompatibility antigens are partially deleted during pregnancy Journal of Immunology  1998 161:2677-2683  PMID:9743323
    • Kench, J. A., Russell, D. M., Nemazee, D. Efficient peripheral clonal elimination of b lymphocytes in mrl/lpr mice bearing autoantibody transgenes Journal of Experimental Medicine  1998 188:909-917  DOI:10.1084/jem.188.5.909  PMID:9730892
    • Hertz, M., Kouskoff, V., Nakamura, T., Nemazee, D. V(d)j recombinase induction in splenic b lymphocytes is inhibited by antigen-receptor signalling Nature  1998 394:292-295  DOI:10.1038/28419  PMID:9685161  PMCID:PMC4523147
    • Hertz, M., Nemazee, D. Receptor editing and commitment in b lymphocytes Current Opinion in Immunology  1998 10:208-213  DOI:10.1016/s0952-7915(98)80250-1  PMID:9602310
    • Melamed, D., Benschop, R. J., Cambier, J. C., Nemazee, D. Developmental regulation of b lymphocyte immune tolerance compartmentalizes clonal selection from receptor selection Cell  1998 92:173-182  DOI:10.1016/s0092-8674(00)80912-5  PMID:9458042
    • Nemazee, D. Theoretical limits to massive receptor editing in immature b cells Current Topics in Microbiology and Immunology  1998 229:163-171  PMID:9479854
    • Pelanda, R., Schwers, S., Sonoda, E., Torres, R. M., Nemazee, D., Rajewsky, K. Receptor editing in a transgenic mouse model: Site, efficiency, and role in b cell tolerance and antibody diversification Immunity  1997 7:765-775  DOI:10.1016/s1074-7613(00)80395-7  PMID:9430222
    • Lang, J., Arnold, B., Hammerling, G., Harris, A. W., Korsmeyer, S., Russell, D., Strasser, A., Nemazee, D. Enforced bcl-2 expression inhibits antigen-mediated clonal elimination of peripheral b cells in an antigen dose-dependent manner and promotes receptor editing in autoreactive, immature b cells Journal of Experimental Medicine  1997 186:1513-1522  DOI:10.1084/jem.186.9.1513  PMID:9348309
    • Papavasiliou, F., Casellas, R., Suh, H. Y., Qin, X. F., Besmer, E., Pelanda, R., Nemazee, D., Rajewsky, K., Nussenzweig, M. C. V(d)j recombination in mature b cells: A mechanism for altering antibody responses Science  1997 278:298-301  DOI:10.1126/science.278.5336.298  PMID:9323210
    • Melamed, D., Nemazee, D. Self-antigen does not accelerate immature b cell apoptosis, but stimulates receptor editing as a consequence of developmental arrest Proceedings of the National Academy of Sciences of the United States of America  1997 94:9267-9272  DOI:10.1073/pnas.94.17.9267  PMID:9256471
    • Melamed, D., Kench, J. A., Grabstein, K., Rolink, A., Nemazee, D. Functional b cell receptor transgene allows efficient il-7-independent maturation of b cell precursors Journal of Immunology  1997 159:1233-1239  PMID:9233618
    • Hertz, M., Nemazee, D. Bcr ligation induces receptor editing in igm(+)igd(-) bone marrow b cells in vitro Immunity  1997 6:429-436  DOI:10.1016/s1074-7613(00)80286-1  PMID:9133422
    • Foster, M. H., Liu, Q. G., Chen, H., Nemazee, D., Cooperstone, B. G. Anti-laminin reactivity and glomerular immune deposition by in vitro recombinant antibodies Autoimmunity  1997 26:231-243  DOI:10.3109/08916939709008029  PMID:9543184
    • Lang, J., Jackson, M., Teyton, L., Brunmark, A., Kane, K., Nemazee, D. B cells are exquisitely sensitive to central tolerance and receptor editing induced by ultralow affinity, membrane-bound antigen Journal of Experimental Medicine  1996 184:1685-1697  DOI:10.1084/jem.184.5.1685  PMID:8920858  PMCID:PMC2192881
    • Rubio, C. F., Kench, J., Russell, D. M., Yawger, R., Nemazee, D. Analysis of central b cell tolerance in autoimmune-prone mrl/lpr mice bearing autoantibody transgenes Journal of Immunology  1996 157:65-71  PMID:8683157
    • Nemazee, D. Can receptor editing play an important role in normal b-cell development? Journal of Autoimmunity  1996 9:259-261  DOI:10.1006/jaut.1996.0032  PMID:8738971
    • Nemazee, D. Antigen receptor 'capacity' and the sensitivity of self-tolerance Immunology Today  1996 17:25-29  DOI:10.1016/0167-5699(96)80565-2  PMID:8652047
    • Spanopoulou, E., Roman, C. A. J., Corcoran, L. M., Schlissel, M. S., Silver, D. P., Nemazee, D., Nussenzweig, M. C., Shinton, S. A., Hardy, R. R., Baltimore, D. Functional immunoglobulin transgenes guide ordered b-cell differentiation in rag-1-deficient mice Genes & Development  1994 8:1030-1042  DOI:10.1101/gad.8.9.1030  PMID:7926785
    • Nemazee, D. Promotion and prevention of autoimmunity by b-lymphocytes Current Opinion in Immunology  1993 5:866-872  DOI:10.1016/0952-7915(93)90098-d  PMID:8297518
    • Tiegs, S. L., Russell, D. M., Nemazee, D. Receptor editing in self-reactive bone-marrow b-cells Journal of Experimental Medicine  1993 177:1009-1020  DOI:10.1084/jem.177.4.1009  PMID:8459201
    • Cuende, E., Kroemer, G., Alonso, J. M., Nemazee, D., Martinez, C., Alesmartinez, J. E. Inability of il-2 and il-10 to counteract b-cell clonal deletion Cellular Immunology  1992 142:94-102  DOI:10.1016/0008-8749(92)90271-p  PMID:1586962
    • Nemazee, D. Mechanisms and meaning of lymphocyte-b tolerance Research in Immunology  1992 143:272-275  DOI:10.1016/s0923-2494(92)80118-5  PMID:1631404
    • Russell, D. M., Dembic, Z., Morahan, G., Miller, Jfap, Burki, K., Nemazee, D. Peripheral deletion of self-reactive b-cells Nature  1991 354:308-311  DOI:10.1038/354308a0  PMID:1956380  PMCID:PMC3787863
    • Nemazee, D., Guiet, C., Buerki, K., Marshakrothstein, A. Lymphocytes-b from the autoimmune-prone mouse strain mlr/1pr manifest an intrinsic defect in tetraparental mrl/1pr reversible dba/2 chimeras Journal of Immunology  1991 147:2536-2539  PMID:1918976
    • Nemazee, D., Russell, D., Arnold, B., Haemmerling, G., Allison, J., Miller, Jfap, Morahan, G., Buerki, K. Clonal deletion of autospecific lymphocytes-b Immunological Reviews  1991 122:117-132  DOI:10.1111/j.1600-065X.1991.tb00600.x  PMID:1937539
    • Carbone, A., Harbeck, R., Dallas, A., Nemazee, D., Finkel, T., Obrien, R., Kubo, R., Born, W. Alpha beta T-lymphocyte depleted mice, a model for gamma delta T-lymphocyte functional studies Immunological Reviews  1991 120:35-50  PMID:1830862  PMCID:PMC4475640
    • Nemazee, D., Buerki, K. Clonal deletion of autoreactive lymphocytes-b in bone-marrow chimeras Proceedings of the National Academy of Sciences of the United States of America  1989 86:8039-8043  DOI:10.1073/pnas.86.20.8039  PMID:2682636
    • Nemazee, D. A., Burki, K. Clonal deletion of lymphocyte-b in a transgenic mouse bearing anti-mhc class-i antibody genes Nature  1989 337:562-566  DOI:10.1038/337562a0  PMID:2783762
    • Shlomchik, M., Nemazee, D., Vansnick, J., Weigert, M. Variable region sequences of murine igm anti-igg monoclonal autoantibodies (rheumatoid factors) .2. Comparison of hybridomas derived by lipopolysaccharide stimulation and secondary protein immunization Journal of Experimental Medicine  1987 165:970-987  DOI:10.1084/jem.165.4.970  PMID:3494096
    • Rammensee, H. G., Julius, M. H., Nemazee, D., Langhorne, J., Lamers, R., Kohler, G. Targeting cytotoxic t-cells to antigen-specific lymphocytes-b European Journal of Immunology  1987 17:433-436  DOI:10.1002/eji.1830170322  PMID:3494614
    • Shlomchik, M. J., Nemazee, D. A., Sato, V. L., Vansnick, J., Carson, D. A., Weigert, M. G. Variable region sequences of murine igm anti-igg monoclonal autoantibodies (rheumatoid factors) - a structural explanation for the high-frequency of igm anti-igg b-cells Journal of Experimental Medicine  1986 164:407-427  DOI:10.1084/jem.164.2.407  PMID:3088205
    • Wysocki, L. J., Margolies, M. N., Huang, B., Nemazee, D. A., Wechsler, D. S., Sato, V. L., Smith, J. A., Gefter, M. L. Combinational diversity within variable regions bearing the predominant anti-rho-azophenylarsonate idiotype of strain-a mice Journal of Immunology  1985 134:2740-2747  PMID:2982953
    • Nemazee, D. A. Immune-complexes can trigger specific, t-cell-dependent, autoanti-igg antibody-production in mice Journal of Experimental Medicine  1985 161:242-256  DOI:10.1084/jem.161.1.242  PMID:2578542
    • Nemazee, D. A., Studer, S., Steinmetz, M., Dembic, Z., Kiefer, M. The lymphoproliferating cells of mrl-lpr/lpr mice are a polyclonal population that bear the lymphocyte-t receptor for antigen European Journal of Immunology  1985 15:760-764  DOI:10.1002/eji.1830150804  PMID:4029256
    • Nemazee, D. A., Sato, V. L. Induction of rheumatoid antibodies in the mouse - regulated production of autoantibody in the secondary humoral response Journal of Experimental Medicine  1983 158:529-545  DOI:10.1084/jem.158.2.529  PMID:6350525
    • Nemazee, D. A., Sato, V. L. Enhancing antibody - a novel component of the immune-response Proceedings of the National Academy of Sciences of the United States of America-Biological Sciences  1982 79:3828-3832  DOI:10.1073/pnas.79.12.3828  PMID:6179088

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Research

research overview

  • 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.

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Teaching

advisees

  • graduate advising relationship

    • Duong, Bao Hoa, Ph.D.  candidate, 2004 - 2009
    • Vela, Jose L, Ph.D.  candidate, 2002 - 2007
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Background

education and training

  • Ph.D. in Cellular and Developmental Biology, Harvard University 1983
  • B.A. in Biochemistry, Harvard University , Harvard College, cum laude 1979
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Contact

full name

  • David Nemazee

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