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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Nov;83(21):8293–8297. doi: 10.1073/pnas.83.21.8293

Fine specificity, idiotypy, and nature of cloned heavy-chain variable region genes of murine monoclonal rheumatoid factor antibodies.

A J Manheimer-Lory, M Monestier, B Bellon, F W Alt, C A Bona
PMCID: PMC386914  PMID: 3095832

Abstract

We investigated the immunochemical and molecular characteristics of murine monoclonal rheumatoid factors. Study of the fine specificity of 20 monoclonal rheumatoid factor antibodies shows a wide degree of heterogeneity. However, many express an interstrain cross-reactive idiotype. We show that our rheumatoid factors utilize a restricted set of the heavy-chain variable region (VH) repertoire representing the more 3' VH families. Preferential expression of 3' VH families is known to occur early in development. We report the nucleotide sequence of two cloned rheumatoid factor VH genes, Y19-10 (VH J558) and 129-48 (VH 7183) in which no major differences are observed between VH genes encoding the heavy chain of autoantibodies and antibodies against foreign antigens.

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Selected References

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  1. Alt F. W., Enea V., Bothwell A. L., Baltimore D. Activity of multiple light chain genes in murine myeloma cells producing a single, functional light chain. Cell. 1980 Aug;21(1):1–12. doi: 10.1016/0092-8674(80)90109-9. [DOI] [PubMed] [Google Scholar]
  2. Alt F. W., Rosenberg N., Enea V., Siden E., Baltimore D. Multiple immunoglobulin heavy-chain gene transcripts in Abelson murine leukemia virus-transformed lymphoid cell lines. Mol Cell Biol. 1982 Apr;2(4):386–400. doi: 10.1128/mcb.2.4.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blackwell T. K., Alt F. W. Site-specific recombination between immunoglobulin D and JH segments that were introduced into the genome of a murine pre-B cell line. Cell. 1984 May;37(1):105–112. doi: 10.1016/0092-8674(84)90305-2. [DOI] [PubMed] [Google Scholar]
  4. Blattner F. R., Williams B. G., Blechl A. E., Denniston-Thompson K., Faber H. E., Furlong L., Grunwald D. J., Kiefer D. O., Moore D. D., Schumm J. W. Charon phages: safer derivatives of bacteriophage lambda for DNA cloning. Science. 1977 Apr 8;196(4286):161–169. doi: 10.1126/science.847462. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Chen P. P., Fong S., Houghten R. A., Carson D. A. Characterization of an epibody. An antiidiotype that reacts with both the idiotype of rheumatoid factors (RF) and the antigen recognized by RF. J Exp Med. 1985 Feb 1;161(2):323–331. doi: 10.1084/jem.161.2.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen P. P., Fong S., Normansell D., Houghten R. A., Karras J. G., Vaughan J. H., Carson D. A. Delineation of a cross-reactive idiotype on human autoantibodies with antibody against a synthetic peptide. J Exp Med. 1984 May 1;159(5):1502–1511. doi: 10.1084/jem.159.5.1502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hartman A. B., Rudikoff S. VH genes encoding the immune response to beta-(1,6)-galactan: somatic mutation in IgM molecules. EMBO J. 1984 Dec 1;3(12):3023–3030. doi: 10.1002/j.1460-2075.1984.tb02249.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. KUNKEL H. G., MULLER-EBERHARD H. J., FUDENBERG H. H., TOMASI T. B. Gamma globulin complexes in rheumatoid arthritis and certain other conditions. J Clin Invest. 1961 Jan;40:117–129. doi: 10.1172/JCI104224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kofler R., Noonan D. J., Levy D. E., Wilson M. C., Møller N. P., Dixon F. J., Theofilopoulos A. N. Genetic elements used for a murine lupus anti-DNA autoantibody are closely related to those for antibodies to exogenous antigens. J Exp Med. 1985 Apr 1;161(4):805–815. doi: 10.1084/jem.161.4.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  12. Margolies M. N., Juszczak E. C., Near R., Marshak-Rothstein A., Rothstein T. L., Sato V. L., Siekevitz M., Smith J. A., Wysocki L. J., Gefter M. L. Structural correlates of idiotypy in the arsonate system. Ann N Y Acad Sci. 1983;418:48–64. doi: 10.1111/j.1749-6632.1983.tb18054.x. [DOI] [PubMed] [Google Scholar]
  13. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  14. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  15. Steffen D., Bird S., Rowe W. P., Weinberg R. A. Identification of DNA fragments carrying ecotropic proviruses of AKR mice. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4554–4558. doi: 10.1073/pnas.76.9.4554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Victor-Kobrin C., Bonilla F. A., Bellon B., Bona C. A. Immunochemical and molecular characterization of regulatory idiotopes expressed by monoclonal antibodies exhibiting or lacking beta 2-6 fructosan binding activity. J Exp Med. 1985 Aug 1;162(2):647–662. doi: 10.1084/jem.162.2.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. White B. A., Bancroft F. C. Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. J Biol Chem. 1982 Aug 10;257(15):8569–8572. [PubMed] [Google Scholar]
  18. Yancopoulos G. D., Desiderio S. V., Paskind M., Kearney J. F., Baltimore D., Alt F. W. Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines. Nature. 1984 Oct 25;311(5988):727–733. doi: 10.1038/311727a0. [DOI] [PubMed] [Google Scholar]

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