Torrey Pines Institute for Molecular Studies science image
Torrey Pines Institute for
Molecular Studies
3550 General Atomics Court, 2-129
San Diego, CA 92121-1122
USA
Scientists
Roy Riblet
Member
Genetics

858.597.3852 - phone
858.597.3804 - fax

Genes that Control the Immune System

Antibody genes -- structure of the immunoglobulin heavy chain locus (Igh)

A thorough understanding of the functional and regulatory roles of antibodies and their genes is important to the development of therapeutic interventions in the immune response. Our goal is to determine the physical structure and DNA sequence of the large complex of antibody heavy chain genes in the mouse; this will create a complete catalog of the sequences that determine antibody binding specificity. This can be compared with the human gene catalog to identify conserved genes that have important protective or regulatory functions. Figure 1 shows a map of this gene complex. The four types of Igh gene segments that are assembled to create a functional heavy chain gene are the Constant region (Ch), Joining region (Jh), Diversity region (Dh), and Variable region (Vh) segments.

Our first goal is to isolate the entire immunoglobulin heavy chain (Igh) gene complex as overlapping clones in Yeast and Bacterial Artificial Chromosomes (YACs and BACs) from two different mouse strains. We have assembled an overlapping array of YAC clones that contain the entire Igh complex from the C57BL/6 and C57BL/10 mouse strains [1, 2]. These gene segments are scattered over 3 million basepairs (3 Mb), and we identified 140 specific genes for sequencing.

The YAC contig map and supporting Southern blots can be seen here:

We have begun to assemble a similar array of BAC clones from the 129/Sv strain that we had previously shown to differ extensively from C57BL/6. This now extends approximately 1.5 Mb and contains about half of the heavy chain genes [3]. In a collaboration with Ann Feeney of The Scripps Research Institute we precisely mapped and sequenced the Vh gene family immediately flanking the Dh region, the Vh7183 family, and analyzed the frequency of rearrangement of each Vh7183 gene [4]. This work revealed that the major determinant of rearrangement frequency of these Vh genes is their proximity to the D, J and C gene segments.

The recent initiation of the Mouse Genome Sequencing Project provided the opportunity to sequence the entire 3 Mb Igh locus of the chosen mouse strain, C57BL/6. Using the extensive mapping information we generated in the above work we were able to rapidly assemble the B6 BAC contig needed for this [5]. Sequencing is now in progress.

Antibody heavy chain genes -- replication

Through a collaboration with Drs. Barbara Birshtein and Carl Schildkraut at Albert Einstein College of Medicine we have characterized the 3' Igh regulatory region (3'RR, Figure 1) that flanks the constant region gene array. This 100 kb region contains important enhancer elements controlling Igh expression and an origin of DNA replication that initiates a 400 kb replicon extending into the Vh gene array. This area had been very difficult to approach with phage cloning, but the BAC clones effectively recovered these important regions of the genome. The replication timing in this region is described in reference 6. Dr. Fumi Matsuda at the Centre National de Genotypage, Evry, France joined this collaboration to accomplish the sequencing of this BAC and the localization of the replication origin to a 2 kb interval [7]. We are extending these studies to investigate replication patterns throughout the Igh locus.

Antibody heavy chain genes -- activation of the Igh locus during B cell differentiation

The replication work above has shown that the pattern of DNA replication in the Igh locus changes remarkably as the cells that express this locus, antibody producing B cells, differentiate and mature. In non-B cells the 400 kb replicon initiating in the 3'RR is apparently the only active origin in this region. As cells commit to the B cell pathway many additional replication origins become active and the 3'RR is not predominant. When B cells reach maturity and are effective antibody producers the replication pattern reverts to the initial simple pattern. Interestingly, these developmental changes in replication pattern appear correlated with changes in nuclear localization of the Igh locus. Fluorescent in situ hybridization (FISH) experiments reveal that the Igh locus moves from a location in the outer portion of the nucleus in non-B cells to a more central location in pro- and pre-B cells. In these differentiating cells the Igh locus becomes activated and undergoes rearrangement of the V, D, and J segments to produce a joined active Ig heavy chain gene. When the cell matures to a functional B cell the Igh locus again shifts to the nuclear periphery [8, 9]. We believe these location changes represent movement from a peripheral area of inactive chromatin to a central area where DNA rearrangement machinery is located, and then to a different peripheral area where active genes are copied into messenger RNA for protein production.

Genes that control stem cells

A second project is to identify and clone Stem Cell Frequency Regulator (Scfr) genes that affect the numbers of hematopoietic (blood forming) stem cells in the bone marrow of mice and men. These stem cells give rise to all the cells of the blood and those of the immune system. Identification of the Scfr genes and their biological functions will provide an important understanding of stem cell biology and provide novel avenues for manipulation of stem cells for therapeutic ends, such as improved bone marrow transplant therapy. This work is being carried out in collaboration with Dr. Christa Muller-Sieburg at the Sidney Kimmel Cancer Center.

The first step in this project was to identify and map two Scfr genes by analyzing Recombinant Inbred mouse strains that had different levels of hematopoietic stem cells [10]. The next phase is to precisely map these Scfr genes so that we can isolate them in YAC and BAC clones. This requires extensive mouse breeding to create a series of "reduced congenic" mouse strains; such strains are created by breeding a chromosomal segment containing a Scfr gene from a high stem cell strain onto a low stem cell strain background. By reducing the size of this donor chromosome segment we can locate the Scfr gene for cloning.

We wanted to investigate the mode of action of these Scfr genes, to see if they acted intrinsically in stem cells, for example by controlling responsiveness to growth signals, or if they exerted their effect extrinsically, for example by affecting the level of growth regulating hormones made by nearby cells. To do this we wanted to create a situation where "high" and "low" strain stem cells coexisted in a common environment subject to the same extrinsic signals. We created tetraparental (4 parent) mice by aggregating 2 day old embryos from Scfr high and low mice and replacing them in the uteri of foster mother mice. The embryos fuse and then develop normally to make chimeras, mixed mice where all tissues are composed of mixtures of the two donor strains. Analysis of the stem cell frequencies of the of the two parental types showed that stem cells from the high strain were more frequent than the low type, that the gene action was almost entirely intrinsic [11].

We have begun to analyze bone marrow cells and enriched subpopulations of high and low stem cell mouse strains by microarray techniques to identify genes that are expressed to different degrees in these mouse strains.

Key References 1-11

  1. Chevillard, C., Ozaki, J., Herring, C.D., and Riblet, R. (2002) A 3 megabase Yeast Artificial Chromosome contig spanning the C57BL/6 mouse Igh locus. J. Immunology, submitted.
  2. Herring, C.D., Chevillard, C., Johnston, S.L., Wettstein, P.J., & Riblet, R. (1998). Vector-hexamer PCR isolation of all insert ends from a YAC contig of the mouse Igh locus. Genome Res, 8(6), 673-81.
  3. Chevillard, C., Mauhar, A., Herring, C. D., Ashouin, N., Birshtein, B. K., and Riblet, R. (2002) A 1.5 Mb BAC contig spanning the 129 mouse Igh-C and proximal Igh-V locus. manuscript in preparation.
  4. Williams, G.S., Martinez, A., Montalbano, A., Tang, A., Mauhar, A., Ogwaro, K.M., Merz, D., Chevillard, C., Riblet, R. and Feeney, A.J. (2001) Unequal VH gene rearrangement frequency within the large VH7183 gene family is not due to RSS variation, and mapping of the genes shows a bias of rearrangement based on chromosomal location. J. Immunology 167: 257.
  5. Riblet, R., Mauhar, A., Chevillard, C., McPherson, J., and Smith, D. (2002) BAC contig of the C57BL/6 mouse Igh locus for sequencing, evolutionary comparisons, and functional studies. manuscript in preparation.
  6. Ermakova, O.V., Nguyen, L.H., Little, R.D., Chevillard, C., Riblet, R., Ashouian, N., Birshtein, B.K. and Schildkraut, C.L. (1999) 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.
  7. Birshtein, B.K., Ashouin, N., Matsuda, F., Chevillard, C., and Riblet, R. (2002) The sequence of a 125 kb BAC 3' adjacent to the IgA locus in mouse contains the origin of replication of the 400 kb Igh replicon, the 3' regulatory region (LCR) and the 3' boundary of the Igh domain. manuscript in preparation.
  8. Zhou, J., Ermakova, O.V., Norio, P., Ashouian, N., Riblet, R., Birshtein, B.K. and Schildkraut, C.L. (2002) Dynamic changes in replication of the Igh locus during B cell development. submitted.
  9. Kosak, S.T., Zhou, J., Skok, J., Le Beau, M.M., Riblet, R., Fisher, A.G., Schildkraut, C., and Singh, H. (2002) Immunoglobulin loci undergo lineage-specific nuclear compartmentalization. submitted.
  10. Muller-Sieburg, C. and Riblet, R. (1996) Genetic Control of the Frequency of Hematopoietic Stem Cells In Mice: Mapping of a Candidate Locus to Chromosome 1. J. Exp. Med. 183: 1141-1150.
  11. Muller-Sieburg, C. E., et al. (2000) Genetic control of hematopoietic stem cell frequency in mice is mostly cell autonomous. Blood 95:2446-2448.

Publications

  1. Jhunjhunwala, S., van Zelm, M., Peak, M., Riblet, R., van Dongen, J., Grosveld, F., Knoch, T., and Murre, C. The 3D-Structure of the Immunoglobulin Heavy Chain Locus: Implications for Long-Range Genomic Interactions. Cell 133:265-79, 2008.
  2. Retter, I., Chevillard, C., Scharfe, M., Conrad, A., Hafner, M., Löhnert, T.-H., Ludewig, M., Nordsiek, G., Severitt, S., Thies, S., Mauhar, A., Blöcker, H., Müller, W. and Riblet, R. Sequence and characterization of the Ig heavy chain constant and partial variable region of the mouse strain 129S1. J. Immunol. 2007 Aug 15;179(4):2419-27.
  3. Pawlitzky, I., Angeles, C.V., Siegel, A.M., Stanton, M.L., Riblet, R., Brodeur, P.H. Identification of a candidate regulatory element within the 5' flanking region of the mouse Igh locus defined by pro-B cell-specific hypersensitivity associated with binding of PU.1, Pax5, and E2A. J. Immunol. 176:6839-6851, 2006.
  4. Norio, P., Kosiyatrakul, S., Yang, Q., Guan, Z., Brown, N., Thomas, S., Riblet, R. and Schildkraut, C. Progressive activation of DNA replication initiation across large domains of the immunoglobulin heavy chain locus during B cell development. Mol. Cell 20:575-587, 2005.
  5. Sayegh, C., Jhunjhunwala, S., Riblet, R. Murre, C. Visualization of looping involving the immunoglobulin heavy-chain locus in developing B cells. Genes Dev. 19:322-327, 2005.
  6. Yang, Q., Riblet, R., Schildkraut, C.L. Sites that direct nuclear compartmentalization are near the 5´ end of the mouse immunoglobulin heavy-chain locus. Mol. Cel. Biol. 25:6021-6030, 2005.
  7. Jones Tiffany, L., Riblet, R., Stein, K.E. The Sr1 gene that controls diversity of the anti-inulin antibody response maps to mouse chromosome 14. Immunogenetics 55:80-86, 2003.
  8. Chevillard, C., Ozaki, J., Herring, C.D., Riblet, R. A three-megabase yeast artificial chromosome contig spanning the C57BL mouse Igh locus. J. Immunol. 168:5659-5666, 2002.
  9. Kosak, S.T., Skok, J.A., Medina, K.L., Riblet, R., LeBeau, M.M., Fisher, A.G., Singh, H. Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science 296:158-162, 2002.
  10. Zhou, J., Ashouian, N., Delepine, M., Matsuda, F., Chevillard, C., Riblet, R., Schildkraut, C.L., Birshtein, B.K. 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 99:13693-13698, 2002.
  11. Zhou, J., Ermakova, O.V., Riblet, R., Birshtein, B.K., Schildkraut, C.L. Replication and sub-nuclear location dynamics of the immunoglobulin heavy-chain locus in B-lineage cells. Mol. Cell. Biol. 22:4876-4889, 2002.
  12. Williams, G.S., Martinez, A., Montalbano, A., Tang, A., Mauhar, A., Ogwaro, K.M., Merz, D., Chevillard, C., Riblet, R., Feeney, A.J. Unequal VH gene rearrangement frequency within the large VH7183 gene family is not due to RSS variation, and mapping of genes shows a bias of rearrangement based on chromosomal location. J. Immunol. 167:257-263, 2001.
  13. Muller-Sieburg, C.E., Cho, R.H., Sieburg, H.B., Kupriyanov, S., Riblet, R. Genetic control of hematopoietic stem cell frequency in mice is mostly cell autonomous. Blood 95:2446-2448, 2000.
  14. D'Eustachio, P., Riblet, R. Mouse chromosome 12. Mamm. Genome, 10:953, 1999.
  15. Ermakova, O.V., Nguyen, L.H., Little, R.D., Chevillard, C., Riblet, R., Ashouian, N., Birshtein, B.K., Schildkraut, C.L. Evidence that a single replication fork proceeds from early to late replicating domains in the IgH locus in a non-B cell line. Mol. Cell 3:321-330, 1999.
  16. Lovchik, J.A., Wilder, J.A., Huffnagle, G.B., Riblet, R., Lyons, C.R., Lipscomb, M.F. Ig heavy chain complex-linked genes influence the immune response in a murine cryptococcal infection. J. Immunol. 163:3907-3913, 1999.
  17. Lund, J., Roe, B., Chen, F., Budarf, M., Galili, N., Riblet, R., Miller, R.D., Emanuel, B.S., Reeves, R.H. Sequence-ready physical map of the mouse chromosome 16 region with conserved synteny to the human velocardiofacial syndrome region on 22q11.2. Mamm. Genome 10:438-443, 1999.
  18. D'Eustachio, P., Riblet, R. Mouse chromosome 12. Mamm. Genome S241:S241-S257, 1998.
  19. Herring, C.D., Chevillard, C., Johnston, S.L., Wettstein, P.J., Riblet, R. Vector-hexamer PCR isolation of all insert ends from a YAC contig of the mouse Igh locus. Genome Res. 8:673-681, 1998.
  20. D'Eustachio, P., Riblet, R. Mouse chromosome 12. Mamm. Genome 7:S209-S222, 1997.
  21. Michaelson, J.S., Ermakova, O., Birshtein, B.K., Ashouian, N., Chevillard, C., Riblet, R., Schildkraut, C.L. Regulation of the replication of the murine immunoglobulin heavy chain gene locus: evaluation of the role of the 3' regulatory region. Mol. Cell. Biol. 17:6167-6174, 1997.
  22. Riblet, R., Tutter, A., Ozaki, J., Herring, C. Genetic tools for the study of immunoglobulin genes and their function. In: Handbook of Experimental Immunology. 5th Edition. D.M. Weir, L.A. Herzenberg, C.C. Blackwell and L.A. Herzenberg, eds. Blackwell Scientific Publications, Ltd., Edinburgh, 1997, pages 3.1-3.3.
  23. D'Eustachio, P., Riblet, R. Mouse chromosome 12. Mamm. Genome 6:S221-S231, 1996.  
  24. Muller-Sieburg, C.E., Riblet, R. Genetic control of the frequency of hematopoietic stem cells in mice: mapping of a candidate locus to chromosome 1. J. Exp. Med. 183:1141-1150, 1996.
  25. Radtkey, R.R., Becker, B., Miller, R.D., Riblet, R., Case, T.J. Variation and evolution of class I MHC in sexual and parthenogenetic geckos. Proc. Roy. Soc. Lond. B 263:1023-1032, 1996.
  26. Miller, R.D., Riblet, R. Improved phenol emulsion DNA reassociation technique (PERT) using thermal cycling. Nucleic Acids Res. 23:2339-2340, 1995.
  27. Miller, R.D., Hogg, J., Ozaki, J.H., Gell, D., Jackson, S.P., Riblet, R. Gene for the catalytic subunit of mouse DNA-dependent protein kinase maps to the scid locus. Proc. Natl. Acad. Sci. USA 92:10792-10795, 1995.
  28. Wettstein, P.J., Strausbauch, M., Lamb, T., States, J., Chakraborty, R., Jin, L., Riblet, R. Phylogeny of six Sciurus aberti subspecies based on nucleotide sequences of cytochrome b. Mol. Phylogenet. Evol. 4:150-162, 1995.
  29. Brait, M., Ryelandt, M., Ismaili, J., Miller, R., Vansantem, G., Riblet, R., Urbain, J. Selection of anti-arsonate idiotype (CRIA) in A/J mice by the immune network. Adv. Exp. Med. Biol. 355:45-49, 1994.
  30. Miller, R.D., Ozaki, J.H., Riblet, R. A backcross panel typed for several immunoglobulin gene superfamily members on MMU9. Mouse Genome 92:694-695, 1994.
  31. Feeney, A.J., Riblet, R. DST4: a new, and probably the last, functional DH gene in the BALB/c mouse. Immunogenetics 37:217-221, 1993.
  32. Miller, R.D., Ozaki, J.H., Riblet, R. The mouse severe combined immune deficiency (scid) mutation is closely linked to the B-cell-specific developmental genes VpreB and lambda 5. Genomics 16:740-744, 1993.
  33. Muralidhar, G., Sepulveda, H., Feeney, A.J., Riblet, R., Dutton, R.W. Restricted IgH V gene usage in the response to the ese epitope on "Hi" sheep red blood cells. J. Immunol. 149:3574-3579, 1992.
  34. Reeves, R.H., Miller, R.D., Riblet, R. Report of the committee on chromosome 16. Mamm. Genome 1:S269-S279, 1991.
  35. Tutter, A., Brodeur, P., Shlomchik, M., Riblet, R. Structure, map position, and evolution of two newly diverged mouse Ig VH gene families. J. Immunol. 147:3215-3223, 1991.
  36. Mertens, F., Berek, C., Andris, F., Willems, F., Brait, M., Miller, R., Riblet, R.J., Slaoui, M., Urbain, J. A private idiotype can become recurrent through genetic recombination and gene(s) unlinked to the Igh locus governs its expression. Eur. J. Immunol. 20:1815-1823, 1990.
  37. Hardy, R.R., Carmack, C.E., Shinton, S.A., Riblet, R.J., Hayakawa, K. A single VH gene is utilized predominantly in anti-BrMRBC hybridomas derived from purified Ly-1 B cells. Definition of the VH11 family. J. Immunol. 142:3643-3651, 1989.
  38. Miller, R.D., Ozaki, J.H., Riblet, R., Gold, D.P. Genetic mapping of murine CD3d and CD3e between Apoa1 and Ncam. Immunogenet. 30:511-514, 1989.
  39. Schreiber, K.L., Webb, C., Tucker, P., Riblet, R., Forman, J. Developmental coupling of expression of the Igh-linked minor antigen H-40 to membrane immunoglobulin expression. Transplantation 48:331-338, 1989.
  40. Tutter, A., Riblet, R. Conservation of an immunoglobulin variable region gene family indicates a unique, non-coding function. Proc. Nat. Acad. Sci. USA 86:7460-7464, 1989.
  41. Tutter, A., Riblet, R. Evolution of the immunoglobulin heavy chain variable region (Igh-V) locus in the genus Mus. Immunogenet. 30:315-329, 1989.
  42. Clayman, M.D., Sun, M.J., Michaud, L., Brill-Dashoff, J., Riblet, R., Neilson, E.G. Clonotypic heterogeneity in experimental interstitial nephritis: Restricted specificity of the anti-tubular basement membrane B cell repertoire is associated with a disease modifying cross-reactive idiotype. J. Exp. Med. 167:1296-1312, 1988.
  43. Tutter, A., Riblet, R. Duplication and deletions of Vh genes in inbred strains of mice. Immunogenet. 28:125-135, 1988.
  44. Tutter, A., Riblet, R. Selective and neutral evolution in the murine Igh-V locus. In: Current Topics in Microbiology and Immunology 137:107-115, 1988.
  45. Moran, T.M., Monestier, M., Lai, A.C., Norton, G., Reale, M.A., Thompson, M.A., Schulman, J.L., Riblet, R., Bona, C.A. Characterization of variable-region genes and shared crossreactive idiotypes of antibodies specific for antigens of various influenza viruses. Viral Immunol. 1:1-12, 1987.
  46. Riblet, R.J., Brodeur, P., Tutter, A., Thompson, M.A. Structure and evolution of the mouse Igh locus. In: Evolution and Vertebrate Immunity: The Antigen-Receptor and MHC Gene Families. G. Kelsoe and D. Schulze, eds. University of Texas Press, pp. 53-61, 1987.
  47. D'Eustachio, P., Kristensen, T., Wetsel, R.A., Riblet, R., Taylor, B.A., Tack, B.F. Chromosomal location of the genes encoding complement components C5 and factor H in the mouse. J. Immunol. 137:3990-3995, 1986.
  48. Riblet, R., Brodeur, P.H. The Igh-V gene repertoire of the mouse. Mt. Sinai J. Med. 53:170-174, 1986.
  49. Riblet, R., Brodeur, P.H. The Igh-V genes of the mouse. In: Handbook of Experimental Immunology. 4th Edition. D.M. Weir, L.A. Herzenberg, C.C. Blackwell and L.A. Herzenberg, eds. Blackwell Scientific Publications, Ltd., Edinburgh, Vol. 3, Chapter 89, 1986.
  50. Baum, C.M., McKearn, J.P., Riblet, R.J., Davie, J.M. Polymorphism of Fc receptor on murine B cells is Igh-linked. J. Exp. Med. 162:282-296, 1985.
  51. Eisenberg, R.A., Riblet, R.J., Lewis, D.E., Cohen, P.L. Spontaneous antiidiotypic antibodies to the NZB Coombs autoantibody. Clin. Exp. Immunol. 62:315-320, 1985.
  52. Roehm, N.W., Carbone, A., Kushir, E., Taylor, B.A., Riblet, R.J., Marrack, P., Kappler, J.W. The major histocompatibility complex-restricted antigen receptor on T cells: The genetics of expression of an allotype. J. Immunol. 135:2176-2182, 1985.
  53. Sherman, L.A., Riblet, R.J. Comparison of the H-2Kb specific CTL receptor repertoire in Igh recombinant strains. J. Immunol. 134:3569-3573, 1985.
  54. Taylor, B.A., Rowe, L., Gibson, D.M., Riblet, R., Yetter, R., Gottlieb, P.D. Linkage of a 7S RNA sequence and kappa light chain genes in the mouse. Immunogenetics 22:471-481, 1985.
  55. Brodeur, P.H., Riblet, R. 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. 14:922-930, 1984.
  56. Brodeur, P.H., Thompson, M.A., Riblet, R.J. The content and organization of mouse Igh-V families. In: Regulation of the Immune System. UCLA Symposia on Molecular and Cellular Biology, New Series, Vol. 18. E. Sercarz, H. Cantor and L. Chess, eds. Alan R. Liss, Inc., New York, New York, 1984. pp. 445-453.
  57. Cancro, M.P., Raychaudhuri, S., Riblet, R.J. Action and genetic restrictions of neonatally induced suppressor T-cells. In: Regulation of the Immune System. UCLA Symposia on Molecular and Cellular Biology, New Series, Vol. 18. E. Sercarz, H. Cantor and L. Chess, eds. Alan R. Liss, Inc., New York, New York, 1984. pp. 789-797.
  58. Forman, J., Riblet, R., Brooks, K., Vitetta, E.S., Henderson, L.A. H-40, an antigen controlled by an Igh linked gene and recognized by cytotoxic T lymphocytes. I. Genetic analysis of H-40 and distribution of its product on B cell tumors. J. Exp. Med. 159:1724-1740, 1984.
  59. Henderson, L.A., Ciavarra, R., Riblet, R.J., Forman, J. H-40, an antigen controlled by an Igh linked gene and recognized by cytotoxic T lymphocytes. II. Recognition of H-40 as a tumor antigen in leukemic animals. J. Immunol. 133:2778-2785, 1984.
  60. O'Toole, M.M., Riblet, R., Bosma, M.J. Identification and mapping of Lm-1, an Igh-linked locus for a murine alloantigen. Immunogenetics 20:265-275, 1984.
  61. Owen, F.L., Riblet, R. Genes for the mouse T cell alloantigens Tpre, Tthy, Tind, and Tsu are closely linked near Igh on chromosome 12. J. Exp. Med. 159:313-317, 1984.
  62. Pincus, S., Carmack, C., Brodeur, P., Riblet, R.J. Antibody degeneracy in the immune response to synthetic polypeptides: Preliminary structural studies. In: Regulation of the Immune System. UCLA Symposia on Molecular and Cellular Biology, New Series, Vol. 18. E. Sercarz, H. Cantor and L. Chess, eds. Alan R. Liss, Inc., New York, New York, 1984. pp. 455-465.
  63. Harris, L.J., Remmers, E.F., Brodeur, P., Riblet, R., D'Eustachio, P., Marcu, K.B. c-myc Gene rearrangements involving gamma immunoglobulin heavy chain gene switch regions in murine plasmacytomas. Nucleic Acids Res. 11:8303-8315, 1983.
  64. Miller, A., Ch'ng, L.K., Benjamin, C., Sercarz, E., Brodeur, P., Riblet, R. Detailed analysis of the public idiotype of anti-hen egg-white lysozyme antibodies. Ann. NY Acad. Sci. 418:140-150, 1983.
  65. Bocchieri, M.H., Cooke, A., Smith, J.B., Weigert, M., Riblet, R.J. Independent segregation of NZB immune abnormalities in NZB x C58 recombinant inbred mice. Eur. J. Immunol. 12:349-354, 1982.
  66. Datta, S.K., Owen, F.L., Womack, J.E., Riblet, R.J. Analysis of recombinant inbred lines derived from "autoimmune" (NZB) and "high leukemia" (C58) strains: independent multigenic systems control B cell hyperactivity, retrovirus expression, and autoimmunity. J. Immunol. 129:1539-1544, 1982.
  67. Owen, F.L., Riblet, R., Gottlieb, P.D. T suppressor cells activated by anti-Tsud serum are Igh-V-restricted. Eur. J. Immunol. 12:94-97, 1982.
  68. Siekevitz, M., Gefter, M.L., Brodeur, P., Riblet, R., Marshak-Rothstein, A. The genetic basis of antibody production: the dominant anti-arsonate idiotype response of the strain A mouse. Eur. J. Immunol. 12:1023-1032, 1982.
  69. Bocchieri, M.H., Riblet, R.J., Smith, J.B. Autologous mixed lymphocyte reactions in NZB mice: Analysis in recombinant inbred lines shows a T cell defect unrelated to auto-antibody production. Eur. J. Immunol. 11:159-162, 1981.
  70. Marshak-Rothstein, A., Margolies, M.N., Riblet, R.J., Gefter, M.L. Specificity of idiotype suppression in the A/J anti-azophenylarsonate system. In: Immunoglobulin Idiotypes. C. Janeway, E.E. Sercarz and H. Wigzell, eds. Academic Press, New York, 1981. pp. 739-749.
  71. Lindahl, K.F., Bocchieri, M.N., Riblet, R.J. Maternally transmitted target antigen for unrestricted killing by NZB T lymphocytes. J. Exp. Med. 152:1583-1595, 1980.
  72. Riblet, R.J., Claflin, L., Gibson, D.M., Mathieson, B.J., Weigert, M. Antibody gene linkage studies in (NZB x C58) recombinant inbred lines. J. Immunol. 124:787-789, 1980.
  73. Loh, E., Black, B., Riblet, R.J., Weigert, M., Hood, J.M., Hood, L. Comparisons of myeloma proteins from NZB and BALB/c mice: Structural and functional differences. Proc. Natl. Acad. Sci. USA 75:1395-1399, 1979.
  74. Loh, E., Hood, J.M., Riblet, R.J., Weigert, M., Hood, L. Comparisons of myeloma proteins from NZB and BALB/c mice: Structural and functional differences of heavy chains. J. Immunol. 122:44-48, 1979.
  75. Zeldis, J.B., Riblet, R.J., Konigsberg, W.H., Richards, F.F., Rosenstein, R.W. The location and expression of idiotypic determinants in the immunoglobulin variable region. III. Expression of the protein 315 and 460 idiotypic determinants in mouse anti-Dnp antibodies. Mol. Immunol. 16:657-664, 1979.
  76. Weigert, M., Riblet, R.J. The genetic control of antibody variable regions in the mouse. In: Springer Seminars in Immunopathology. B. Benacerraf, ed. 1:133-169, 1978.
  77. Riblet, R.J. The organization of antibody genes. In: Immune System: Genetics and Regulation. E.E. Sercarz, L.A. Herzenberg and C.F. Fox, eds. Academic Press, New York, 1977. pp. 83-89.
  78. Watson, J., Riblet, R., Taylor, B.A. The response of recombinant inbred strains of mice to bacterial lipopolysaccharides. J. Immunol. 118:2088-2093, 1977.
  79. Weigert, M., Riblet, R. Genetic control of antibody variable regions. Cold Spring Harb. Symp. Quant. Biol. 2:837-846, 1977.
  80. Skidmore, B.J., Chiller, J.M., Weigle, W.O., Riblet, R., Watson, J. Immunologic properties of bacterial lipopolysaccharide (LPS). III. Genetic linkage between the in vitro mitogenic and in vivo adjuvant properties of LPS. J. Exp. Med. 143:143-150, 1976.
  81. Watson, J., Riblet, R., Cohn, M., Skidmore, B.J., Chiller, J.M., Weigle, W.O. The mitogenic activity of bacterial lipopolysaccharide as a probe for T cell function. In: Oppenheim, J.J., Rosenstreich, D.L., ed. Mitogens in Immunobiology. New York, Academic Press, 605(2)., pp. 245-60, 1976.
  82. Riblet, R., Blomberg, B., Weigert, M., Lieberman, R., Taylor, B.A., Potter, M. Genetics of mouse antibodies. I. Linkage of the dextran response locus, VH-DEX, to allotype. Eur. J. Immunol. 5:775-777, 1975.
  83. Riblet, R., Weigert, M., Makela, O. Genetics of mouse antibodies. II. Recombination between VH genes and allotype. Eur. J. Immunol. 5:778-781, 1975.
  84. Taylor, B.A., Bailey, D.W., Cherry, M., Riblet, R., Weigert, M. Genes for immunoglobulin heavy chain and serum prealbumin protein are linked in mouse. Nature 256:644-646, 1975.
  85. Trenkner, E., Riblet, R. Induction of antiphosphorylcholine antibody formation by anti-idiotypic antibodies. J. Exp. Med. 142:1121-1132, 1975.
  86. Watson, J., Riblet, R. Genetic control of responses to bacterial lipopolysaccharides in mice. II. A gene that influences a membrane component involved in the activation of bone marrow-derived lymphocytes by lipipolysaccharides. J. Immunol. 114:1462-1468, 1975.
  87. Cohn, M., Blomberg, B., Geckeler, W., Raschke, W., Riblet, R.J., Weigert, M. First order considerations in analyzing the generator for diversity. In: The Immune System - Genes, Receptors, Signals. E.E. Sercarz, A.R. Williamson and C.F. Fox, eds. Academic Press, New York, 1974. pp. 89-117.
  88. Riblet, R.J. Sequence studies of mouse lysozyme. In: Lysozyme. E.F. Osserman, R.E. Canfield and S. Beychok, eds. Academic Press, New York, 1974. pp. 89-93.
  89. Watson, J., Riblet, R. Genetic control of responses to bacterial lipopolysaccharides in mice. I. Evidence for a single gene that influences mitogenic and immunogenic respones to lipopolysaccharides. J. Exp. Med. 140:1147-1161, 1974.
  90. Herzenberg, L.A., Chan, E.L., Ravitch, M.M., Riblet, R.J., Herzenberg, L.A. Active suppression of immunoglobulin allotype synthesis. 3. Identification of T cells as responsible for suppression by cells from spleen, thymus, lymph node, and bone marrow. J. Exp. Med. 137:1311-1324, 1973.
  91. Jacobson, E.B., Herzenberg, L.A., Riblet, R., Herzenberg, L.A. Active suppression of immunoglobulin allotype synthesis. II. Transfer of suppressing factor with spleen cells. J. Exp. Med. 135:1163-1176, 1972.
  92. Herzenberg, L.A., Jacobson, E.B., Riblet, R.J. Chronic allotype suppression in mice: an active regulatory process. Ann. NY Acad. Sci. 190:212-20, 1971.
  93. Riblet, R.J., Herzenberg, L.A. Mouse lysozyme production by a monocytoma: isolation and comparison with other lysozymes. Science 168:1595-1597, 1970.
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