Abstract
Using mAb that selectively recognize the various allelic forms of the VHT15 and Vk21D-E genes' products, we analyzed the influence of VH and Vk polymorphism on the probability of expression of these gene segments. Our data show that the frequency to which the VHT15 gene product becomes available in the preimmune repertoire is strongly influenced by the polymorphism of the relevant structural gene, suggesting therefore that VH genes cannot be randomly used in the various strains. Contrary to this, the frequency of Vk21D-E+ clones is similar in all mouse strains tested, and in all cases is higher than the frequency of VHT15 clones. This observation strongly suggests that Vk genes can be randomly expressed, and/or that their number is lower than that of their VH counterpart. Finally, analysis of the specificity associated to the expression of the VHT15 segment revealed that VH polymorphism strongly influences not only the probability of expression of each V gene, but also the specificity of the antibodies on which these VH genes are used.
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- Adams J. M., Kemp D. J., Bernard O., Gough N., Webb E., Tyler B., Gerondakis S., Cory S. Organization and expression of murine immunoglobulin genes. Immunol Rev. 1981;59:5–32. doi: 10.1111/j.1600-065x.1981.tb00454.x. [DOI] [PubMed] [Google Scholar]
- Berek C., Griffiths G. M., Milstein C. Molecular events during maturation of the immune response to oxazolone. Nature. 1985 Aug 1;316(6027):412–418. doi: 10.1038/316412a0. [DOI] [PubMed] [Google Scholar]
- Brack C., Hirama M., Lenhard-Schuller R., Tonegawa S. A complete immunoglobulin gene is created by somatic recombination. Cell. 1978 Sep;15(1):1–14. doi: 10.1016/0092-8674(78)90078-8. [DOI] [PubMed] [Google Scholar]
- 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. 1984 Oct;14(10):922–930. doi: 10.1002/eji.1830141012. [DOI] [PubMed] [Google Scholar]
- Claflin J. L., Davie J. M. Clonal nature of the immune response to phosphorylcholine. III. Species-specific binding characteristics of rodent anti-phosphorylcholine antibodies. J Immunol. 1974 Dec;113(6):1678–1684. [PubMed] [Google Scholar]
- Claflin J. L., Davie J. M. Clonal nature of the immune response to phosphorylcholine. IV. Idiotypic uniformity of binding site-associated antigenic determinants among mouse antiphosphorylcholine antibodies. J Exp Med. 1974 Sep 1;140(3):673–686. doi: 10.1084/jem.140.3.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clarke S. H., Claflin J. L., Potter M., Rudikoff S. Polymorphism in anti-phosphocholine antibodies reflecting evolution of immunoglobulin families. J Exp Med. 1983 Jan 1;157(1):98–113. doi: 10.1084/jem.157.1.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cory S., Tyler B. M., Adams J. M. Sets of immunoglobulin V kappa genes homologous to ten cloned V kappa sequences: implications for the number of germline V kappa genes. J Mol Appl Genet. 1981;1(2):103–116. [PubMed] [Google Scholar]
- Crews S., Griffin J., Huang H., Calame K., Hood L. A single VH gene segment encodes the immune response to phosphorylcholine: somatic mutation is correlated with the class of the antibody. Cell. 1981 Jul;25(1):59–66. doi: 10.1016/0092-8674(81)90231-2. [DOI] [PubMed] [Google Scholar]
- Desaymard C., Giusti A. M., Scharff M. D. Rat anti-T15 monoclonal antibodies with specificity for VH- and VH-VL epitopes. Mol Immunol. 1984 Oct;21(10):961–967. doi: 10.1016/0161-5890(84)90154-8. [DOI] [PubMed] [Google Scholar]
- Devaux C., Labit C., Marchetto S., Pierres M. Shared idiotope on monoclonal anti-Ia.7 antibodies reactive with determinants in a structural domain of the I-E molecules. J Immunol. 1984 Mar;132(3):1353–1360. [PubMed] [Google Scholar]
- Devaux C., Moinier D., Mazza G., Guo X. J., Marchetto S., Fougereau M., Pierres M. Preferential expression of VK21E light chains on IdX Ia.7 positive monoclonal anti-I-E antibodies. J Immunol. 1985 Jun;134(6):4024–4030. [PubMed] [Google Scholar]
- Gearhart P. J., Sigal N. H., Klinman N. R. Production of antibodies of identical idiotype but diverse immunoglobulin classes by cells derived from a single stimulated B cell. Proc Natl Acad Sci U S A. 1975 May;72(5):1707–1711. doi: 10.1073/pnas.72.5.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gibson D. M. Evidence for 65 electrophoretically distinct groups of light chains in BALB/c and NZB myelomas. Mol Immunol. 1984 May;21(5):421–432. doi: 10.1016/0161-5890(84)90040-3. [DOI] [PubMed] [Google Scholar]
- Gibson D. M., Maclean S. J., Cherry M. Recombination between kappa chain genetic markers and the Lyt-3 locus. Immunogenetics. 1983;18(2):111–116. doi: 10.1007/BF00368538. [DOI] [PubMed] [Google Scholar]
- Gottlieb P. D. Genetic correlation of a mouse light chain variable region marker with a thymocyte surface antigen. J Exp Med. 1974 Nov 1;140(5):1432–1437. doi: 10.1084/jem.140.5.1432. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gottlieb P. D., Tsang H. C., Gibson D. M., Cannon L. E. Unique V kappa group associated with two mouse L chain genetic markers. Proc Natl Acad Sci U S A. 1981 Jan;78(1):559–563. doi: 10.1073/pnas.78.1.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Honjo T., Nakai S., Nishida Y., Kataoka T., Yamawaki-Kataoka Y., Takahashi N., Obata M., Shimizu A., Yaoita Y., Nikaido T. Rearrangements of immunoglobulin genes during differentiation and evolution. Immunol Rev. 1981;59:33–67. doi: 10.1111/j.1600-065x.1981.tb00455.x. [DOI] [PubMed] [Google Scholar]
- Huppi K., Jouvin-Marche E., Scott C., Potter M., Weigert M. Genetic polymorphism at the kappa chain locus in mice: comparisons of restriction enzyme hybridization fragments of variable and constant region genes. Immunogenetics. 1985;21(5):445–457. doi: 10.1007/BF00430928. [DOI] [PubMed] [Google Scholar]
- Kemp D. J., Tyler B., Bernard O., Gough N., Gerondakis S., Adams J. M., Cory S. Organization of genes and spacers within the mouse immunoglobulin VH locus. J Mol Appl Genet. 1981;1(3):245–261. [PubMed] [Google Scholar]
- Kenny J. J., Yaffe L. J., Ahmed A., Metcalf E. S. Contribution of Lyb 5+ and Lyb 5- B cells to the primary and secondary phosphocholine-specific antibody response. J Immunol. 1983 Jun;130(6):2574–2579. [PubMed] [Google Scholar]
- Lieberman R., Potter M., Mushinski E. B., Humphrey W., Jr, Rudikoff S. Genetics of a new IgVH (T15 idiotype) marker in the mouse regulating natural antibody to phosphorylcholine. J Exp Med. 1974 Apr 1;139(4):983–1001. doi: 10.1084/jem.139.4.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mosier D. E., Mond J. J., Goldings E. A. The ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an X-linked B cell defect. J Immunol. 1977 Dec;119(6):1874–1878. [PubMed] [Google Scholar]
- Near R. I., Juszczak E. C., Huang S. Y., Sicari S. A., Margolies M. N., Gefter M. L. Expression and rearrangement of homologous immunoglobulin VH genes in two mouse strains. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2167–2171. doi: 10.1073/pnas.81.7.2167. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ozato K., Mayer N., Sachs D. H. Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. J Immunol. 1980 Feb;124(2):533–540. [PubMed] [Google Scholar]
- Potter M., Newell J. B., Rudikoff S., Haber E. Classification of mouse VK groups based on the partial amino acid sequence to the first invariant tryptophan: impact of 14 new sequences from IgG myeloma proteins. Mol Immunol. 1982 Dec;19(12):1619–1630. doi: 10.1016/0161-5890(82)90273-5. [DOI] [PubMed] [Google Scholar]
- Press J. L. The CBA/N defect defines two classes of T cell-dependent antigens. J Immunol. 1981 Apr;126(4):1234–1240. [PubMed] [Google Scholar]
- Primi D., Mami F., Le Guern C., Cazenave P. A. Mitogen-reactive B cell subpopulations selectively express different sets of V regions. J Exp Med. 1982 Jul 1;156(1):181–190. doi: 10.1084/jem.156.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rajewsky K., Takemori T. Genetics, expression, and function of idiotypes. Annu Rev Immunol. 1983;1:569–607. doi: 10.1146/annurev.iy.01.040183.003033. [DOI] [PubMed] [Google Scholar]
- Riblet R., Claflin L., Gibson D. M., Mathieson B. J., Weigert M. Antibody gene linkage studies in (NZB X C58) recombinant-inbred lines. J Immunol. 1980 Feb;124(2):787–789. [PubMed] [Google Scholar]
- Rudikoff S., Claflin J. L. Expression of equivalent clonotypes in BALB/c and A/J mice after immunization with phosphorylcholine. J Exp Med. 1976 Nov 2;144(5):1294–1304. doi: 10.1084/jem.144.5.1294. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rudikoff S., Potter M. Allelic forms of the immunoglobulin heavy chain variable region. J Immunol. 1980 May;124(5):2089–2092. [PubMed] [Google Scholar]
- 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. 1982 Dec;12(12):1023–1032. doi: 10.1002/eji.1830121208. [DOI] [PubMed] [Google Scholar]
- Siekevitz M., Huang S. Y., Gefter M. L. The genetic basis of antibody production: a single heavy chain variable region gene encodes all molecules bearing the dominant anti-arsonate idiotype in the strain A mouse. Eur J Immunol. 1983 Feb;13(2):123–132. doi: 10.1002/eji.1830130207. [DOI] [PubMed] [Google Scholar]
- Stein K. E., Zopf D. A., Miller C. B., Johnson B. M., Mongini P. K., Ahmed A., Paul W. E. Immune response to a thymus-dependent form of B512 dextran requires the presence of Lyb-5+ lymphocytes. J Exp Med. 1983 Feb 1;157(2):657–666. doi: 10.1084/jem.157.2.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wood C., Tonegawa S. Diversity and joining segments of mouse immunoglobulin heavy chain genes are closely linked and in the same orientation: implications for the joining mechanism. Proc Natl Acad Sci U S A. 1983 May;80(10):3030–3034. doi: 10.1073/pnas.80.10.3030. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhu D., Lefkovits I., Köhler G. Frequency of expressed immunoglobulin light chain genes in lipopolysaccharide-stimulated BALB/c spleen cells. J Exp Med. 1984 Oct 1;160(4):971–986. doi: 10.1084/jem.160.4.971. [DOI] [PMC free article] [PubMed] [Google Scholar]
