Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Immune Tolerance and an Extracellular Regulatory Role for Bivalent Antibody

Nature volume 202, pages 677–682 (1964)Cite this article

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Ehrlich, P., and Morgenroth, J., Ber. Klin. Wchschr., 21, 453 (1900).

    Google Scholar 

  2. Burnet, F. M., The Clonal Selection Theory of Acquired Immunity (Vanderbilt Univ. Press, Nashville, Tenn., 1959).

    Book  Google Scholar 

  3. Owen, R. D., Science, 102, 400 (1945).

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Billingham, R. E., Brent, L., and Medawar, P. B., Phil. Trans. Roy. Soc., B, 239, 357 (1956).

    Article  ADS  Google Scholar 

  5. Chase, M. W., Ann. Rev. Microbiol., 13, 349 (1959).

    Article  Google Scholar 

  6. Mitchison, N. A., Immunol., 5, 341 (1962).

    CAS  Google Scholar 

  7. Dresser, D. W., Immunol., 5, 378 (1962).

    CAS  Google Scholar 

  8. Sercarz, E. E., and Coons, A. H., J. Immunol., 90, 478 (1963); Nature, 184, 1080 (1959).

    CAS  PubMed  Google Scholar 

  9. Siskind, G. W., Paterson, P. Y., and Thomas, L., J. Immunol., 90, 929 (1963).

    CAS  PubMed  Google Scholar 

  10. That is, antibody with the same specificity at each of the two sites in the molecule.

  11. Because of the low level of antibody with which we are concerned in the initial phase of the immune response, the concentrations of complexes molar ratios of antibody to antigen greater than one will be negligible. The fact that in antibody-excess complexes of this kind (AgAb n; n > 1) the immunogenicity of th antigen is reduced, or even abolished entirely (refs. 12, 13), is not relevant to this part of the present discussion. However, complexes of the Ab-excess type could provide an important source of control for limiting the amount of antibody formed against one antigen. That is, when antibody-levels become of sufficient magnitude, antibody-excess complexes would be expected to reduce, or eliminate, the antigen's immunogenicity and to hasten its elimination Teleonomically speaking, such a control mechanism could protect an animal trom committing so much of its antibody-forming capacity to one antigen that it is unable to respond to other antigens.

  12. Uhr, J. W., and Baumann, J. B., J. Exp. Med., 113, 935 (1961).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Downie, A. W., Glenny, A. T., Parish, H. J., Smith, W., and Wilson, G. S., Brit. Med. J., ii, 717 (1941).

  14. Glenny, A. T., and Hopkins, B. E., J. Hygiene, 21, 142 (1923).

    Article  Google Scholar 

  15. Terres, G., and Wolins, W., Proc. Soc. Exp. Biol. and Med., 102, 632 (1959).

    Article  CAS  Google Scholar 

  16. Segre, D., and Kaeberle, M. L., J. Immunol., 89, 782 (1962).

    CAS  PubMed  Google Scholar 

  17. Monod, J., Changeaux, J.-P., and Jacob, F. J., J. Mol. Biol., 6, 306 (1963).

    Article  CAS  PubMed  Google Scholar 

  18. Haurowitz, F., and Schwerin, P., J. Immunol., 47, 111 (1943).

    CAS  Google Scholar 

  19. Eisen, H. N., Carsten, M. E., and Belman, S., J. Immunol., 73, 296 (1954).

    CAS  PubMed  Google Scholar 

  20. Nisonoff, A., Winkler, M. H., and Pressman, D., J. Immunol., 82, 201 (1959).

    CAS  PubMed  Google Scholar 

  21. Smith, R. T., Adv. Immunol., 1, 67 (1961).

    Article  CAS  Google Scholar 

  22. In view of the importance ascribed to bivalence it is necessary to consider the possible role of monovalent antibody. The monovalence of antibody is not an established experimental fact. The view that such antibody exists, although not incompatible with our present knowledge, is nevertheless an unwarranted inference from the existence of non-precipitating antibody. In addition, it is not necessary to our hypothesis that every antibody molecule be able to form an inductive complex. As is suggested by the differences between blocking and skin-sensitizing antibodies in human allergy, and between γ2 and γ1 7S guinea pig antibodies (refs. 22, 23), different antibody molecules directed against the same antigenic determinant may differ in their capacity for cellular attachment.

  23. Fireman, P., Vannier, W. E., and Goodman, H. C., J. Exp. Med., 117, 603. (1963).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ovary, Z., Benacerraf, B., and Bloch, K. J., J. Exp. Med., 117, 951 (1963).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Pauling, L., J. Amer. Chem. Soc., 62, 2643 (1940).

    Article  CAS  Google Scholar 

  26. Lederberg, J., Science, 129, 1649 (1959).

    Article  ADS  CAS  PubMed  Google Scholar 

  27. Karush, F., in Immunochemical Approaches to Problems in Microbiology, edit. by Heidelberger, M., and Plescia, O. J. (Rutgers Univ. Press, New Brunswick, New Jersey, 1961).

    Google Scholar 

  28. Hoerlein, A. B., J. Immunol., 78, 112 (1957).

    CAS  PubMed  Google Scholar 

  29. Jerne, N. K., Proc. U.S. Nat. Acad. Sci., 41, 849 (1955).

    Article  ADS  CAS  Google Scholar 

  30. Boyden, S. V., Nature, 185, 724 (1960).

    Article  ADS  CAS  PubMed  Google Scholar 

  31. Uhr, J. W., Finklestein, M. S., and Baumann, J. B., J. Exp. Med., 115, 655 (1962).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Karush, F., Adv. Immunol., 2, 1 (1962).

    CAS  Google Scholar 

  33. Thorbecke, G. J., Siskind, G. W., and Goldberger, N., J. Immunol., 87, 147 (1961).

    CAS  PubMed  Google Scholar 

  34. Terres, G., and Hughes, W. L., J. Immunol., 83, 459 (1959).

    CAS  PubMed  Google Scholar 

  35. Martinez, C., Smith, J. M., Blaese, M., and Good, R. A., J. Exp. Med., 118, 743 (1963).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Main, J. M., and Prehn, R. T., J. Nat. Cancer Inst., 15, 1023 (1955).

    CAS  PubMed  Google Scholar 

  37. Schwartz, R. S., and Dameshek, W., J. Immunol., 90, 703 (1963).

    CAS  PubMed  Google Scholar 

  38. Martinez, C., Shapiro, F., Kelman, H., Onstad, T., and Good, R. A., Proc. Soc. Exp. Biol. and Med., 103, 266 (1960).

    Article  CAS  Google Scholar 

  39. Martinez, C., Smith, J. M., Blaese, M., and Good, R. A., Fed. Proc., 22, 441 (1963).

    Google Scholar 

  40. Smith, R. T., and Bridges, R. A., J. Exp. Med., 108, 227 (1958).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. McMaster, P. D., and Kruse, H., J. Exp. Med., 94, 323 (1951).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Garvey, J. S., and Campbell, D. H., J. Exp. Med., 105, 361 (1957).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Cohen, S., Halloway, R. C., Matthews, C., and McFarlane, A. S., Biochem. J., 62, 133 (1956).

    Article  Google Scholar 

  44. Berson, S. A., Yalow, R. S., Schreiber, S. S., and Post, J., J. Clin. Invest., 32, 746 (1953).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cinader, B., and Dubert, J. M., Proc. Roy. Soc., B, 146, 18 (1956).

    Article  ADS  CAS  Google Scholar 

  46. Weigle, W. O., J. Exp. Med., 114, 111 (1961).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Newton, W. T., Fed. Proc., 22, 440 (1963).

    Google Scholar 

  48. Curtin, C. C., Brit. J. Exp. Path., 40, 255 (1958).

    Google Scholar 

  49. Bussard, A., and Hannoun, C., Nature, 194, 881 (1962).

    Article  ADS  CAS  PubMed  Google Scholar 

  50. Kaplan, M., J. Immunol., 80, 254, 268 (1958).

    CAS  PubMed  Google Scholar 

  51. Nossal, G. J. V., Adv. Immunol., 2, 163 (1962).

    Article  Google Scholar 

  52. Urso, P., and Makinodan, T., J. Immunol., 90, 897 (1963).

    CAS  PubMed  Google Scholar 

  53. Harris, T. N., and Harris, S., in Mechanisms of Hypersensitivity, edit. by Shaffer, J. H., LoGrippo, G. A., and Chase, M. W., 575 (Little, Brown and Co., Boston, 1959).

    Google Scholar 

  54. Najarian, J. S., and Feldman, J. D., J. Exp. Med., 115, 1083 (1962).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Karush, F., and Eisen, H. N., Science, 136, 1032 (1962).

    Article  ADS  CAS  PubMed  Google Scholar 

  56. Dixon, F. J., and Maurer, P., J. Exp. Med., 101, 245 (1955).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Mitchison, N. A., in Mechanism of Immunological Tolerance, 245 (Czech. Acad. Sci., Prague, 1962).

    Google Scholar 

  58. Billingham, R. E., Silvers, W. K., and Wilson, D. B., J. Exp. Med., 118, 397 (1963).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Simonsen, M., in Mechanisms of Immunological Tolerance (Czech. Acad. Sci., Prague, 1962).

    Google Scholar 

  60. Hilgard, H., Burnet, D., and Burnet, F. M., Austral. J. Exp. Biol. And Med., 40, 233 (1962).

    Article  CAS  Google Scholar 

  61. Martinez, C., Shapiro, F., and Good, R. A., Proc. Soc. Exp. Biol. and Med., 107, 553 (1961).

    Article  CAS  Google Scholar 

  62. Argyris, B. F., J. Immunol., 90, 29 (1963).

    CAS  PubMed  Google Scholar 

  63. Mitchison, N. A. (personal communication).

  64. Dietrich, F. M., and Weigle, W. O. (in the press).

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology, Washington University School of Medicine, St. Louis, Missouri

    HERMAN N. EISEN &  FRED KARUSH

  2. Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia

    HERMAN N. EISEN &  FRED KARUSH

Authors
  1. HERMAN N. EISEN
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. FRED KARUSH
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

EISEN, H., KARUSH, F. Immune Tolerance and an Extracellular Regulatory Role for Bivalent Antibody. Nature 202, 677–682 (1964). https://doi.org/10.1038/202677a0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/202677a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing