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. 1987 Feb;79(2):572–581. doi: 10.1172/JCI112849

Idiotypic markers of polyclonal B cell activation. Public idiotypes shared by monoclonal antibodies derived from patients with systemic lupus erythematosus or leprosy.

C Mackworth-Young, J Sabbaga, R S Schwartz
PMCID: PMC424130  PMID: 3492514

Abstract

We investigated idiotypic markers of monoclonal antibodies derived from patients with polyclonal B-cell activation. Four monoclonal antibodies with different ligand binding specificities derived from a patient with lepromatous leprosy and three monoclonal anti-DNA antibodies from two patients with SLE were studied. Three new public idiotopes, which were common to monoclonal antibodies from all three patients, were defined by five polyclonal rabbit antiidiotypes, two monoclonal mouse antiidiotopes, and a monoclonal mouse antibody against a synthetic peptide that contains residues of the heavy chain CDR-1 of a monoclonal lupus anti-DNA antibody. The antibody against the synthetic idiotype was found to react with native immunoglobulins in solution. One idiotope was found to be consistently immunogenic in all animals tested. Since the three patients are of different ethnic origins, these shared idiotypes are probably encoded by germline V genes. These genes may be recurrently expressed in states of polyclonal B-cell activation, regardless of etiology. The results suggest that some autoantibodies arise by expansion of a pool of precursors in the normal antibody repertoire.

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Selected References

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

  1. Andrews D. W., Capra J. D. Complete amino acid sequence of variable domains from two monoclonal human anti-gamma globulins of the Wa cross-idiotypic group: suggestion that the J segments are involved in the structural correlate of the idiotype. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3799–3803. doi: 10.1073/pnas.78.6.3799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andrzejewski C., Jr, Stollar B. D., Lalor T. M., Schwartz R. S. Hybridoma autoantibodies to DNA. J Immunol. 1980 Mar;124(3):1499–1502. [PubMed] [Google Scholar]
  3. Atkinson P. M., Lampman G. W., Furie B. C., Naparstek Y., Schwartz R. S., Stollar B. D., Furie B. Homology of the NH2-terminal amino acid sequences of the heavy and light chains of human monoclonal lupus autoantibodies containing the dominant 16/6 idiotype. J Clin Invest. 1985 Apr;75(4):1138–1143. doi: 10.1172/JCI111808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cairns E., Block J., Bell D. A. Anti-DNA autoantibody-producing hybridomas of normal human lymphoid cell origin. J Clin Invest. 1984 Sep;74(3):880–887. doi: 10.1172/JCI111505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carson D., Weigert M. Immunochemical analysis of the cross-reacting idiotypes of mouse myeloma proteins with anti-dextran activity and normal anti-dextran antibody. Proc Natl Acad Sci U S A. 1973 Jan;70(1):235–239. doi: 10.1073/pnas.70.1.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Chen P. P., Houghten R. A., Fong S., Rhodes G. H., Gilbertson T. A., Vaughan J. H., Lerner R. A., Carson D. A. Anti-hypervariable region antibody induced by a defined peptide: an approach for studying the structural correlates of idiotypes. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1784–1788. doi: 10.1073/pnas.81.6.1784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Datta S. K., Naparstek Y., Schwartz R. S. In vitro production of an anti-DNA idiotype by lymphocytes of normal subjects and patients with systemic lupus erythematosus. Clin Immunol Immunopathol. 1986 Mar;38(3):302–318. doi: 10.1016/0090-1229(86)90240-0. [DOI] [PubMed] [Google Scholar]
  9. Datta S. K., Stollar B. D., Schwartz R. S. Normal mice express idiotypes related to autoantibody idiotypes of lupus mice. Proc Natl Acad Sci U S A. 1983 May;80(9):2723–2727. doi: 10.1073/pnas.80.9.2723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Diamond B., Solomon G. A monoclonal antibody that recognizes anti-DNA antibodies in patients with systemic lupus. Ann N Y Acad Sci. 1983;418:379–385. doi: 10.1111/j.1749-6632.1983.tb18087.x. [DOI] [PubMed] [Google Scholar]
  11. GREY H. M., MANNIK M., KUNKEL H. G. INDIVIDUAL ANTIGENIC SPECIFICITY OF MYELOMA PROTEINS. CHARACTERISTICS AND LOCALIZATION TO SUBUNITS. J Exp Med. 1965 Apr 1;121:561–575. doi: 10.1084/jem.121.4.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hoch S., Schwaber J. Specificity analysis of human anti-DNA antibodies. J Immunol. 1986 Feb 1;136(3):892–897. [PubMed] [Google Scholar]
  13. Isenberg D. A., Collins C. Detection of cross-reactive anti-DNA antibody idiotypes on renal tissue-bound immunoglobulins from lupus patients. J Clin Invest. 1985 Jul;76(1):287–294. doi: 10.1172/JCI111959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Isenberg D. A., Shoenfeld Y., Madaio M. P., Rauch J., Reichlin M., Stollar B. D., Schwartz R. S. Anti-DNA antibody idiotypes in systemic lupus erythematosus. Lancet. 1984 Aug 25;2(8400):417–422. doi: 10.1016/s0140-6736(84)92904-0. [DOI] [PubMed] [Google Scholar]
  15. Isenberg D., Dudeney C., Wojnaruska F., Bhogal B. S., Rauch J., Schattner A., Naparstek Y., Duggan D. Detection of cross reactive anti-DNA antibody idiotypes on tissue-bound immunoglobulins from skin biopsies of lupus patients. J Immunol. 1985 Jul;135(1):261–264. [PubMed] [Google Scholar]
  16. Jacob L., Tron F., Lety M. A., Bach J. F. Idiotypes of monoclonal anti-DNA antibodies produced in autoimmune B/W mice are expressed in normal mice. Clin Exp Immunol. 1986 Feb;63(2):402–407. [PMC free article] [PubMed] [Google Scholar]
  17. Kindt T. J., Seide R. K., Bokisch V. A., Krause R. M. Detection of idiotypic cross-reactions among streptococcal antisera from related rabbits. J Exp Med. 1973 Sep 1;138(3):522–537. doi: 10.1084/jem.138.3.522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kunkel H. G., Agnello V., Joslin F. G., Winchester R. J., Capra J. D. Cross-idiotypic specificity among monoclonal IgM proteins with anti- -globulin activity. J Exp Med. 1973 Feb 1;137(2):331–342. doi: 10.1084/jem.137.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kunkel H. G. Experimental approaches tohomogenous antibody populations. iIndividual antigenic specificity, cross specificity and diversity of human antibodies. Fed Proc. 1970 Jan-Feb;29(1):55–58. [PubMed] [Google Scholar]
  20. Kunkel H. G., Mannik M., Williams R. C. Individual Antigenic Specificity of Isolated Antibodies. Science. 1963 Jun 14;140(3572):1218–1219. doi: 10.1126/science.140.3572.1218. [DOI] [PubMed] [Google Scholar]
  21. Lefvert A. K., James R. W., Alliod C., Fulpius B. W. A monoclonal anti-idiotypic antibody against anti-receptor antibodies from myasthenic sera. Eur J Immunol. 1982 Sep;12(9):790–792. doi: 10.1002/eji.1830120917. [DOI] [PubMed] [Google Scholar]
  22. Lieberman R., Vrana M., Humphrey W., Jr, Chien C. C., Potter M. Idiotypes of inulin-binding myeloma proteins localized to variable region light and heavy chains: genetic significance. J Exp Med. 1977 Nov 1;146(5):1294–1304. doi: 10.1084/jem.146.5.1294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Masala C., Amendolea M. A., Nuti M., Riccarducci R., Tarabini C. G., Tarabini C. G. Autoantibodies in leprosy. Int J Lepr Other Mycobact Dis. 1979 Jun;47(2):171–175. [PubMed] [Google Scholar]
  24. McMillan S., Seiden M. V., Houghten R. A., Clevinger B., Davie J. M., Lerner R. A. Synthetic idiotypes: the third hypervariable region of murine anti-dextran antibodies. Cell. 1983 Dec;35(3 Pt 2):859–863. doi: 10.1016/0092-8674(83)90118-6. [DOI] [PubMed] [Google Scholar]
  25. Morgan A., Isenberg D. A., Naparstek Y., Rauch J., Duggan D., Khiroya R., Staines N. A., Schattner A. Shared idiotypes are expressed on mouse and human anti-DNA autoantibodies. Immunology. 1985 Nov;56(3):393–399. [PMC free article] [PubMed] [Google Scholar]
  26. OUDIN J., MICHEL M. [A new allotype form of rabbit serum gamma-globulins, apparently associated with antibody function and specificity]. C R Hebd Seances Acad Sci. 1963 Jul 17;257:805–808. [PubMed] [Google Scholar]
  27. Oudin J., Cazenave P. A. Similar idiotypic specificities in immunoglobulin fractions with different antibody functions or even without detectable antibody function. Proc Natl Acad Sci U S A. 1971 Oct;68(10):2616–2620. doi: 10.1073/pnas.68.10.2616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rauch J., Massicotte H., Tannenbaum H. Specific and shared idiotypes found on hybridoma anti-DNA autoantibodies derived from rheumatoid arthritis and systemic lupus erythematosus patients. J Immunol. 1985 Oct;135(4):2385–2392. [PubMed] [Google Scholar]
  29. Reichlin M. Use of glutaraldehyde as a coupling agent for proteins and peptides. Methods Enzymol. 1980;70(A):159–165. doi: 10.1016/s0076-6879(80)70047-2. [DOI] [PubMed] [Google Scholar]
  30. Schiff C., Boyer C., Milili M., Fougereau M. The idiotypy of the MOPC 173 (IgG2a) mouse myeloma protein: characterization of syngeneic, allogeneic and xenogeneic anti-idiotypic antibodies. Contribution of the H and L chains to the idiotypic determinants. Eur J Immunol. 1979 Nov;9(11):831–841. doi: 10.1002/eji.1830091102. [DOI] [PubMed] [Google Scholar]
  31. Seiden M. V., Clevinger B., McMillan S., Srouji A., Lerner R., Davie J. M. Chemical synthesis of idiotopes. Evidence that antisera to the same JH1 peptide detect multiple binding site-associated idiotopes. J Exp Med. 1984 May 1;159(5):1338–1350. doi: 10.1084/jem.159.5.1338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shoenfeld Y., Hsu-Lin S. C., Gabriels J. E., Silberstein L. E., Furie B. C., Furie B., Stollar B. D., Schwartz R. S. Production of autoantibodies by human-human hybridomas. J Clin Invest. 1982 Jul;70(1):205–208. doi: 10.1172/JCI110595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Shoenfeld Y., Isenberg D. A., Rauch J., Madaio M. P., Stollar B. D., Schwartz R. S. Idiotypic cross-reactions of monoclonal human lupus autoantibodies. J Exp Med. 1983 Sep 1;158(3):718–730. doi: 10.1084/jem.158.3.718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Shoenfeld Y., Rauch J., Massicotte H., Datta S. K., André-Schwartz J., Stollar B. D., Schwartz R. S. Polyspecificity of monoclonal lupus autoantibodies produced by human-human hybridomas. N Engl J Med. 1983 Feb 24;308(8):414–420. doi: 10.1056/NEJM198302243080802. [DOI] [PubMed] [Google Scholar]
  35. Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]
  36. Walport M. J., Black C. M., Batchelor J. R. The immunogenetics of SLE. Clin Rheum Dis. 1982 Apr;8(1):3–21. [PubMed] [Google Scholar]
  37. Wang A. C., Wilson K. S., Hopper J. E., Fudenberg H. H., Nisonoff A. Evidence for control of synthesis of the varible regions of the heavy chains of immunoglobulins G and M by the same gene. Proc Natl Acad Sci U S A. 1970 Jun;66(2):337–343. doi: 10.1073/pnas.66.2.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. van Eden W., Gonzalez N. M., de Vries R. R., Convit J., van Rood J. J. HLA-linked control of predisposition to lepromatous leprosy. J Infect Dis. 1985 Jan;151(1):9–14. doi: 10.1093/infdis/151.1.9. [DOI] [PubMed] [Google Scholar]

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