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Roy Riblet

Roy RibletTorreyPinesInstituteCA

Adjunct Member 858.597.3852 - phone
858.597.3804 - fax
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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.

Education

  • 1960-1964: California Institute of Technology, Pasadena, CA      B.S.  (Biology)
  • 1964-1971: Stanford University, Stanford, CA   Ph.D. (Genetics)

Positions

  • 1971-1974   Postdoctoral Fellow, The Salk Institute for Biological Studies, San Diego, CA
  • 1974-1985   Research Associate, Assistant Member, Associate Member, Member, The Institute for Cancer Research, Philadelphia, PA
  • 1978-1985   Member, Genetics Graduate Group, Faculty of Arts and Sciences, University of Pennsylvania, Philadelphia, PA
  • 1983-1987   Member, Allergy and Immunology Study Section, DRG, National Institutes of Health, Bethesda, Maryland
  • 1985-1998   Member, Medical Biology Institute, La Jolla, CA
  • 1987-2009   Editorial Board, Immunogenetics
  • 1998-present      Member, Torrey Pines Institute for Molecular Studies, San Diego, CA

Honors & Awards

  • 1971-1973   Damon Runyon Fellowship
  • 1973-1975   Leukemia Society of America Special Fellowship

Selected Publications (10 of 100)

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.

The mouse immunoglobulin heavy chain (Igh) complex locus is composed of more than 100 gene segments encoding the variable, diversity, joining and constant portions of the antibody heavy chain protein. To advance the characterization of this locus and to identify all the Vh genes, we have isolated the entire region from C57BL/6 and C57BL/10 as a Yeast Artificial Chromosome (YAC) contig.

The mouse Igh locus extends approximately three megabases and contains at least 134 Vh genes classified in 15 partially interspersed families. Two non-Igh pseudogenes (Odc-rs8 and Rpl32-rs14) were localized in the distal part of the locus. This physical YAC map will provide important structure and guidance for the sequencing of this large, complex and highly repetitive locus.

YAC Contig
(Click on image for a more detailed view)

A Table (PDF format) listing the sources, sizes, and end sequences with GenBank accessions is HERE

The Southern blots of the YAC panels probed with various Igh probes are below

Southern blots of Igh locus YACs
(click on link below to open image in a new window)

centromere
O
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//
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| Cmu (IgM) film 3201
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| Jh [pJ11] film 3204
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| Dh [DFL16.1] film 3139
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| Vh7183 [81X] film 2120
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| VhQ52 film 2112
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| VhS107 film 2253
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| VhSM7 film 2323
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| VhX24 film 2190 film2195
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| Vh11 film 2204
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| Vh36-60 film 2076
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| VhVGam3-8 film 2169
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| Vh3609N film 3137
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| Vh12 film 2177
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| VhJ606 film 2315
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| Vh10 film 2303
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| Vh15 film
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| Vh3609P film 2308
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| VhJ558 film 3318
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| Ocd-rs8 film 2613
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| Rpl32-rs14 film 2648
|
//
|
*
telomere

This is a guide to the Southern blots of the set of Yeast Artificial Chromosomes (YACs) that contain the mouse Immunoglobulin Heavy Chain (Igh) locus, as described in Chevillard et al. "A 3 megabase Yeast Artificial Chromosome contig spanning the C57BL mouse Igh locus."

To the left is a schematic map of the Igh locus. The Southern blots showing the content of each gene or family of genes for constant region (C), Joining region (Jh), Diversity region (Dh), and Variable region (Vh) segments in the YACs are identified by "film number". In each blot figure the (EcoRI digested) YACs are listed across the top, and marker sizes are listed on the side. Clicking on the film number will open the blot image.