Genetic and Environmental Control of B-Cell Idiotype Expression

  • Dorith Zharhary
  • Richard L. Riley
  • Barbara G. Froscher
  • Norman R. Klinman


Since the earliest demonstrations that the immune system of an individual has the capacity to recognize its own antibody variable regions, the potential role of such anti-idiotypic recognition in the regulation of immune responses has gained considerable attention(1,2)Studies which have utilized the passive transfer of anti-idiotypic antibodies have defined several levels at which anti-idiotypic recognition can affect immune responsiveness.(3–12) These include the inhibition of antigenic stimulation of idiotype-positive cells,(3–5)the direct stimulation of idiotype-positive cells,(5–8) the elimination of B cells of the appropriate idiotype from within the mature B-cell repertoire(9,10) and the enhancement of the expression of idiotype-positive cells(11,12) Finally, the physiological relevance of idiotypic recognition has been demonstrated by the finding that such recognition becomes a predominant feature of the immune system subsequent to immunization.(13)


Spleen Cell Aged Mouse Antigenic Stimulation Environmental Antigen Antiidiotypic Antibody 
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  1. 1.
    Rodkey, L. S., 1974, Studies of idiotypic antibodies: Production and characterization of auto-anti-idiotypic antiserum, J. Exp. Med. 139:712–720.PubMedCrossRefGoogle Scholar
  2. 2.
    Jerne, N., 1971, Toward a network theory of the immune system, Ann. Immunol. (Paris) 125:373–389.Google Scholar
  3. 3.
    Kohler, H., 1975, The response to phosphorylcholine: Dissecting an immune response, Transplant. Rev. 27:24–56.PubMedGoogle Scholar
  4. 4.
    Hart, D. A., Wang, A. L., Pawlak, L. L., and Nisonoff, A., 1972, Suppression of idiotypic specificities in adult mice by administration of antiidiotypic antibody, J. Exp. Med. 135:1293–1300.PubMedCrossRefGoogle Scholar
  5. 5.
    Eichmann, K., 1978, Expression and function of idiotypes on lymphocytes,Adv. Immunol. 26:194–254.Google Scholar
  6. 6.
    Trenkner, E., and Riblet, R., 1975, Induction of antiphosphorylcholine antibody formation by anti-idiotypic antibodies J Exp. Med. 142:1121–1132.PubMedCrossRefGoogle Scholar
  7. 7.
    Kelsoe, G., Reth, M., and Rajewsky, K., 1980, Control of idiotype expression by monoclonal anti-idiotypic antibodies,Immunol. Rev. 52:75–88.PubMedCrossRefGoogle Scholar
  8. 8.
    Bluestone, J. A., Auchincloss, H., Jr., Cazenave, P.-A., Ozato, K., and Sachs, D. H., 1982, Anti-idiotypes to monoclonal anti-H-2 antibodies. III. Syngeneic anti-idiotypes detect idiotypes on antibodies induced by in vivo administration of xenogeneic anti-idiotypes, J.Immunol. 129:2066–2068.PubMedGoogle Scholar
  9. 9.
    Accolla, R. S., Gearhart, P. J., Sigal, N. H., Cancro, M. P., and Klinman, N. R., 1977, Idiotype-specific neonatal suppression of phosphorylcholine responsive B cells, Eur. J. Immunol. 7:876–881.PubMedCrossRefGoogle Scholar
  10. 10.
    Kohler, H., Kaplan, D., Kaplan, R., Fung, J., and Quintans, J., 1979, Ontogeny of clonal dominance, in:Cells of Immunoglobulin Synthesis (B. Pernis and H. J. Vogel, eds.), Academic Press, New York, pp. 357- 369.Google Scholar
  11. 11.
    Hiernaux, J., Bona, C., and Baker, P. J., 1981, Neonatal treatment with low doses of anti-idiotypic antibody leads to the expression of a silent clone,f. Exp. Med.153:1004–1008.CrossRefGoogle Scholar
  12. 12.
    Rubenstein, L. J., Yeh, M., and Bona, C., 1982, Idiotype-anti-idiotype network. II. Activation of silent clones by treatment at birth with idiotypes is associated with the expansion of idiotype-specific helper T cells,J.Exp. Med. 156:506–520.CrossRefGoogle Scholar
  13. 13.
    Pierce, S. K., and Klinman, N. R., 1977, Antibody specific immunoregulation,J.Exp. Med.146:509–519.PubMedCrossRefGoogle Scholar
  14. 14.
    Makinodan, T., 1970, Age related changes in antibody forming capacity, in:Tolerance, Autoimmunity and Aging (M. M. Sigel and R. A. Good, eds.), Thomas, Springfield, 111., pp. 3–17.Google Scholar
  15. 15.
    Callard, R. E., Basten, A., and Waters, L. K., 1977, Immune function in aged mice. II. B cell functionCell Immunol.31:26–36.PubMedCrossRefGoogle Scholar
  16. 16.
    Zharhary, D., Segev, Y., and Gershon, H., 1977, The affinity and spectrum of cross-reactivity of antibody production in senescent mice: The IgM responseMech. Ageing Dev.6:385–392.PubMedCrossRefGoogle Scholar
  17. 17.
    Krosgrud, R. L., and Perkins, E. H., 1977, Age related changes in T cell functionJ. Immunol.118:1607- 1611.Google Scholar
  18. 18.
    Segre, D., and Segre, M., 1976, Humoral immunity in aged mice. II. Increased suppressor T cell activity in immunologically deficient old miceJ. Immunol.116:735–738.PubMedGoogle Scholar
  19. 19.
    Goidl, E. A., Innes, J. B., and Weksler, M. E., 1976, Immunological studies of aging. II. Loss of IgG and high avidity plaque-forming cells and increased suppressor activity in aging miceJ. Exp. Med.144:1037- 1048.PubMedCrossRefGoogle Scholar
  20. 20.
    Klinman, N. R., 1981, Antibody-specific immunoregulation and the immunodeficiency of agingJ. Exp. Med.154:547–551.PubMedCrossRefGoogle Scholar
  21. 21.
    Kishimoto, S., Takahima, S., and Mizumachi, H., 1976In vitroimmune response to the 2,4,6-trinitro- phenyl determinant in aged C57BL/6J mice: Changes in the humoral immune response to, avidity for the TNP determinant and responsiveness to LPS effect with agingJ. Immunol.116:294–300.PubMedGoogle Scholar
  22. 22.
    Flood, P. M., Urban, J. L., Kripke, M. L., and Schreiber, H., 1981, Loss of tumor-specific immunity with ageJ. Exp. Med.154:275–290.PubMedCrossRefGoogle Scholar
  23. 23.
    Szewczuk, M. R., and Campbell, J. R., 1980, Loss of immune competence with age may be due to auto- anti-idiotypic antibody regulationNature 286:164–166.PubMedCrossRefGoogle Scholar
  24. 24.
    Siskind, G. W., Goidl, E. A., Schrater, A. F., Thorbecke, G. J., and Weksler, M. E., 1982, The role of auto-anti-idiotype antibody in the regulation of the immune responseCell. Immunol.66:34–42.PubMedCrossRefGoogle Scholar
  25. 25.
    Zharhary, D., and Klinman, N., 1983, Antigen responsiveness of the mature and generative B cell populations of aged miceJ. Exp. Med.157:1300–1308.PubMedCrossRefGoogle Scholar
  26. 26.
    Klinman, N. R., and Stone, M. R., 1983, The role of variable region gene expression and environmental selection in determining the anti-phosphorylcholine B cell repertoire.J. Exp. Med.158:1948.PubMedCrossRefGoogle Scholar
  27. 27.
    Etlinger, H. M., 1981, The origin of immunological networks, in:The Immune System: Festschrift in Honor of Niels Kaj feme on the Occasion of His 70th BirthdayVolume I (C. M. Steinberg and I. Lefkovits, eds.), Karger, Basel, pp. 14–20.Google Scholar
  28. 28.
    Denis, K. A., and Klinman, N. R., 1983, The genetic and temporal control of neonatal antibody expressionJ. Exp. Med.157:1170–1183.PubMedCrossRefGoogle Scholar
  29. 29.
    Klinman, N. R., Schrater, A. F., and Katz, D. H., 1981, Immature B cells as the target forin vitrotolerance inductionJ.Immunol.126:1970–1973.PubMedGoogle Scholar
  30. 30.
    Cancro, M. P., Gerhard, W., and Klinman, N. R., 1978, Diversity of the primary influenza specific B cell repertoire in BALB/c miceJ.Exp. Med.147:776–787.PubMedCrossRefGoogle Scholar
  31. 31.
    Cancro, M. P., Wylie, D. E., Gerhard, W., and Klinman, N. R., 1979, Patterned acquisition of the antibody repertoireProc. Natl. Acad. Sci.USA 76:6577–6581.PubMedCrossRefGoogle Scholar
  32. 32.
    Wylie, D. E., and Klinman, N. R., 1981, Assessing repertoire diversity in precursors to mature B cells, in:Proceedings of the Second International Conference on B lymphocytes in the Immune Response(N. R. Klinman, E. Mosier, I. Scher, and E. Vitetta, eds.), Elsevier/North-Holland, Amsterdam, pp. 63–68.Google Scholar
  33. 33.
    Riley, R. L., Wylie, D. E., and Klinman, N. R., 1983, B cell repertoire diversification precedes immunoglobulin receptor expressionf. Exp. Med.158:1733.CrossRefGoogle Scholar
  34. 34.
    Lieberman, R., Potter, M., Mushinski, W., Humphrey, W., Jr., and Rudikoff, S., 1974, Genetics of a new IgVn (T15 idiotype) marker in the mouse regulating natural antibody to phosphorylcholineJ. Exp. Med.139:983–1001.PubMedCrossRefGoogle Scholar
  35. 35.
    Blomberg, B., Geckeler, W., and Weigert, M., 1972, Genetics of the antibody response to dextran in miceScience 177:178–180.PubMedCrossRefGoogle Scholar
  36. 36.
    Makela, O., and Karajalainen, K., 1977, Inherited immunoglobulin idiotypes of the mouseImmunol. Rev.34:119–138.PubMedCrossRefGoogle Scholar
  37. 37.
    Stashenko, P., and Klinman, N. R., 1980, Analysis of the primary anti-NP responseJ. Immunol.125:531- 537.PubMedGoogle Scholar
  38. 38.
    Klinman, N. R., Riley, R. L., Stone, M. R., Wylie, D. E., and Zharhary, D., 1983, The specificity repertoire of pre-receptor and mature B cells, in:Proceedings of the International Conference on Immune Networks.(C. A. Bona and H. Kohler, eds.) Annals of New York Academy of Sciences. 418:130–139.Google Scholar
  39. 39.
    Riley, R. L., and Klinman, N. R. NP-specific repertoires of pre-receptor (slg~) and mature B cells. Fed. Proc. 42:941 (Abstr.)Google Scholar
  40. 40.
    Froscher, B. G., and Klinman, N. R., Immunoregulation in the development of the Dex-specific B cell repertoire in BALB/c mice, (submitted).Google Scholar
  41. 41.
    Nishikawa, S., Toshitada, T., and Rajewsky, K., 1983, The expression of a set of antibody variable regions in lipopolysaccharide-reactive B cells at various stages of ontogeny and its control by anti-idiotypic antibodyEur. f. Immunol.13:318–325.CrossRefGoogle Scholar
  42. 42.
    Juy, D., Primi, D., Sanchez, P., and Cazenave, P. A., 1983, The selection and maintenance of the V region determinant repertoire is germ-line encoded and T cell independentEur. f. Immunol.13:326–331.CrossRefGoogle Scholar
  43. 43.
    Cancro, M. P., Sigal, N. H., and Klinman, N. R., 1978, Differential expression of an equivalent clonotype among BALB/c and C57BL/6 micef. Exp. Med.147:1–12.CrossRefGoogle Scholar
  44. 44.
    Sigal, N. H., 1982, Regulation of azophenylarsonate-specific repertoire expression. I. Frequency of cross- reactive idiotype positive B cells in A/J and BALB/c micef. Exp. Med.156:1352–1365.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Dorith Zharhary
    • 1
  • Richard L. Riley
    • 1
  • Barbara G. Froscher
    • 1
  • Norman R. Klinman
    • 1
  1. 1.Department of ImmunologyScripps Clinic and Research FoundationLa JollaUSA

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