The survival of complex organisms like ourselves is dependent on an immune system that wards off bacteria and viruses that infect and kill. The immune system is multifaceted, involving innate mechanisms that recognize shared general patterns on bacteria and fungi, and adaptive mechanisms that rapidly create novel and highly specific receptors for any foreign structure. In the adaptive arm B lymphocytes invent and produce antibodies, proteins circulating in the bloodstream, that bind to and inactivate bacteria and viruses.
We study basic mechanisms of the antibody response to infectious microorganisms. We are trying to understand how B cells activate their immunoglobulin (Ig) genes to produce novel, specific antibodies. We have found that the process of activating the Ig genes involves large changes in several important things, 1) their location in the nucleus and what structures they are associated with, 2) the time during the cell cycle that the genes are copied which relates to their availability for expression, and 3) their shape and structure. We are pursuing each of these findings to reveal more of how the immune system works. Increased knowledge of the basic mechanisms of immunity will provide novel avenues for therapeutic intervention, to enhance responses to infections, to modulate inappropriate responses to foreign tissue grafts or to components of self in autoimmunity as in multiple sclerosis or diabetes.
- 1964 - 1971: Stanford University, Stanford, CA Ph.D. (Genetics)
- 1960 - 1964: California Institute of Technology, Pasadena, CA B.S. (Biology)
- 1998 - present: Member, Torrey Pines Institute for Molecular Studies, San Diego, CA
- 1987 - 2009: Editorial Board, Immunogenetics
- 1985 - 1998: Member, Medical Biology Institute, La Jolla, CA
- 1983 - 1987: Member, Allergy and Immunology Study Section, DRG, National Institutes of Health, Bethesda, Maryland
- 1978 - 1985: Member, Genetics Graduate Group, Faculty of Arts and Sciences, University of Pennsylvania, Philadelphia, PA
- 1974 - 1985: Research Associate, Assistant Member, Associate Member, Member, The Institute for Cancer Research, Philadelphia, PA
- 1971 - 1974: Postdoctoral Fellow, The Salk Institute for Biological Studies, San Diego, CA
Selected Publications (10 of 100)
- Brodeur, PH, Riblet, RJ. The immunoglobulin heavy chain variable region (Igh-V) locus in the mouse. I. One hundred Igh-V genes comprise seven families of homologous genes. Eur J Immunol. 14:922-30, 1984.
- Chevillard, C, Ozaki, J, Herring, CD, Riblet, R. A Three-Megabase Yeast Artificial Chromosome contig spanning the C57BL mouse Igh locus. J Immunology. 168:5659-66, 2002.
- Retter, I, Chevillard, C, Scharfe, M, Conrad, A, Hafner, M, Löhnert, TH, Ludewig, M, Nordsiek, G, Severitt, S, Thies, S, Mauhar, A, Blöcker, H, Müller, W, Riblet, R. Sequence and characterization of the Ig heavy chain constant and partial variable region of the mouse strain 129S1. J Immunol. 179(4):2419-27, 2007, PMCID: PMC2771210.
- Ermakova, OV, Nguyen, LH, Little, RD, Chevillard, C, Riblet, R, Ashouian, N, Birshtein, BK. Schildkraut, CL. Evidence that a Single Replication Fork Proceeds from Early to Late Replicating Domains in the IgH locus in a non-B cell line. Molecular Cell. 3:1-20, 1999.
- Zhou J, Ashouian N, Delepine M, Matsuda F, Chevillard C, Riblet R, Schildkraut CL, Birshtein BK. The origin of a developmentally regulated Igh replicon is located near the border of regulatory domains for Igh replication and expression. Proc Natl Acad Sci USA. 99:13693-8, 2002, PMCID: PMC129745.
- Norio, P, Kosiyatrakul, S, Yang, Q, Guan, Z, Brown, N, Thomas, S, Riblet, R, Schildkraut, C. Progressive activation of DNA replication initiation across large domains of the immunoglobulin heavy chain locus during B cell development. Mol Cell. 20:575-87, 2005.
- Kosak, ST, Skok, JA, Medina, KL, Riblet, R, Le Beau, MM, Fisher, AG, Singh, H. Subnuclear Compartmentalization of Immunoglobulin Loci During Lymphocyte Development. Science. 296:158-62, 2002.
- Yang, Q, Riblet, R, Schildkraut, CL. Sites that direct nuclear compartmentalization are near the 5´ end of the mouse immunoglobulin heavy-chain locus. Mol Cel Biol. 25:6021-30, 2005, PMCID: PMC1168801.
- Sayegh, C, Jhunjhunwala, S, Riblet, R, Murre, C. Visualization of looping involving the immunoglobulin heavy-chain locus in developing B cells. Genes Dev. 19:322-7, 2005, PMCID: PMC546510.
- Jhunjhunwala, S, van Zelm, M, Peak, M, Riblet, R, van Dongen, J, Grosveld, F, Knoch, T, Murre, C. The 3D-Structure of the Immunoglobulin Heavy Chain Locus: Implications for Long-Range Genomic Interactions. Cell. 133:265-79, 2008, PMCID: PMC2771211.
- 1973 - 1975: Leukemia Society of America Special Fellowship
- 1971 - 1973: Damon Runyon Fellowship