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. 1987 Nov 1;166(5):1456–1463. doi: 10.1084/jem.166.5.1456

Somatically mutated forms of a major anti-p-azophenylarsonate antibody variable region with drastically reduced affinity for p-azophenylarsonate. By-products of an antigen-driven immune response?

T Manser, B Parhami-Seren, MN Margolies, ML Gefter
PMCID: PMC2189635  PMID: 3681190

Abstract

The pivotal role played by antigen in the clonal selection of B cells for initial participation in an immune response is well established. Antigen selective mechanisms ensure that antigen-binding antibodies are produced during all stages of the immune response. However, antibodies that lack specificity for the immunogen might also be produced during the course of an antigen-driven immune response . It has been suggested that, through idiotype-antiidiotype network interactions within the immune system, production of antibodies that lack specificity for the immunogen but that share idiotopes with antigen-binding antibodies could result (1). In addition, data obtained by a number of investigators suggest that somatic mutation of antibody V region genes occurs at a rate of 10(-3)/basepair/cell division in B cells participating in an immune response (2, 3). One outcome of such V region structural alteration could be antibodies that lack, or have drastically reduced affinity for the immunogen . We sought to identify and characterize some of the antibody by-products of the antigen-driven immune response that are expected to be created by the mechanisms described above.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cebra J. J., Komisar J. L., Schweitzer P. A. CH isotype 'switching' during normal B-lymphocyte development. Annu Rev Immunol. 1984;2:493–548. doi: 10.1146/annurev.iy.02.040184.002425. [DOI] [PubMed] [Google Scholar]
  2. Gridley T., Margolies M. N., Gefter M. L. The association of various D elements with a single-immunoglobulin VH gene segment: influence on the expression of a major cross-reactive idiotype. J Immunol. 1985 Feb;134(2):1236–1244. [PubMed] [Google Scholar]
  3. Herzenberg L. A., Black S. J., Tokuhisa T., Herzenberg L. A. Memory B cells at successive stages of differentiation. Affinity maturation and the role of IgD receptors. J Exp Med. 1980 May 1;151(5):1071–1087. doi: 10.1084/jem.151.5.1071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
  5. Jeske D. J., Jarvis J., Milstein C., Capra J. D. Junctional diversity is essential to antibody activity. J Immunol. 1984 Sep;133(3):1090–1092. [PubMed] [Google Scholar]
  6. Juszczak E., Near R. I., Gefter M. L., Margolies M. N. Complete heavy and light chain variable region sequence of anti-arsonate monoclonal antibodies from BALB/c and A/J mice sharing the 36-60 idiotype are highly homologous. J Immunol. 1984 Nov;133(5):2603–2609. [PubMed] [Google Scholar]
  7. Kaartinen M., Griffiths G. M., Hamlyn P. H., Markham A. F., Karjalainen K., Pelkonen J. L., Mäkelä O., Milstein C. Anti-oxazolone hybridomas and the structure of the oxazolone idiotype. J Immunol. 1983 Feb;130(2):937–945. [PubMed] [Google Scholar]
  8. Landolfi N. F., Capra J. D., Tucker P. W. Germ-line sequence of the DH segment employed in Ars-A antibodies: implications for the generation of junctional diversity. J Immunol. 1986 Jul 1;137(1):362–365. [PubMed] [Google Scholar]
  9. Manser T., Gefter M. L. Isolation of hybridomas expressing a specific heavy chain variable region gene segment by using a screening technique that detects mRNA sequences in whole cell lysates. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2470–2474. doi: 10.1073/pnas.81.8.2470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Manser T., Gefter M. L. The molecular evolution of the immune response: idiotope-specific suppression indicates that B cells express germ-line-encoded V genes prior to antigenic stimulation. Eur J Immunol. 1986 Nov;16(11):1439–1444. doi: 10.1002/eji.1830161120. [DOI] [PubMed] [Google Scholar]
  11. Manser T., Huang S. Y., Gefter M. L. Influence of clonal selection on the expression of immunoglobulin variable region genes. Science. 1984 Dec 14;226(4680):1283–1288. doi: 10.1126/science.6334361. [DOI] [PubMed] [Google Scholar]
  12. Margolies M. N., Marshak-Rothstein A., Gefter M. L. Structural diversity among anti-p-azophenylarsonate monoclonal antibodies from A/J mice; comparison of Id- and Id+ sequences. Mol Immunol. 1981 Dec;18(12):1065–1077. doi: 10.1016/0161-5890(81)90022-5. [DOI] [PubMed] [Google Scholar]
  13. McKean D., Huppi K., Bell M., Staudt L., Gerhard W., Weigert M. Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin. Proc Natl Acad Sci U S A. 1984 May;81(10):3180–3184. doi: 10.1073/pnas.81.10.3180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sharon J., Gefter M. L., Manser T., Ptashne M. Site-directed mutagenesis of an invariant amino acid residue at the variable-diversity segments junction of an antibody. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2628–2631. doi: 10.1073/pnas.83.8.2628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Shlomchik M. J., Nemazee D. A., Sato V. L., Van Snick J., Carson D. A., Weigert M. G. Variable region sequences of murine IgM anti-IgG monoclonal autoantibodies (rheumatoid factors). A structural explanation for the high frequency of IgM anti-IgG B cells. J Exp Med. 1986 Aug 1;164(2):407–427. doi: 10.1084/jem.164.2.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sigal N. H. Regulation of azophenylarsonate-specific repertoire expression. 1. Frequency of cross-reactive idiotype-positive B cells in A/J and BALB/c mice. J Exp Med. 1982 Nov 1;156(5):1352–1365. doi: 10.1084/jem.156.5.1352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Smith J. A., Margolies M. N. Complete amino acid sequence of the heavy-chain variable region from an A/J mouse antigen-nonbinding monoclonal antibody bearing the predominant arsonate idiotype. Biochemistry. 1984 Sep 25;23(20):4726–4732. doi: 10.1021/bi00315a031. [DOI] [PubMed] [Google Scholar]
  18. Wysocki L. J., Gridley T., Huang S., Grandea A. G., 3rd, Gefter M. L. Single germline VH and V kappa genes encode predominating antibody variable regions elicited in strain A mice by immunization with p-azophenylarsonate. J Exp Med. 1987 Jul 1;166(1):1–11. doi: 10.1084/jem.166.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wysocki L. J., Sato V. L. The strain A anti-p-azophenylarsonate major cross-reactive idiotypic family includes members with no reactivity toward p-azophenylarsonate. Eur J Immunol. 1981 Oct;11(10):832–839. doi: 10.1002/eji.1830111016. [DOI] [PubMed] [Google Scholar]
  20. Wysocki L., Manser T., Gefter M. L. Somatic evolution of variable region structures during an immune response. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1847–1851. doi: 10.1073/pnas.83.6.1847. [DOI] [PMC free article] [PubMed] [Google Scholar]

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