Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1983 May 1;157(5):1635–1645. doi: 10.1084/jem.157.5.1635

Production of auto-antiidiotypic antibody during the normal immune response. VII. Analysis of the cellular basis for the increased auto- antiidiotype antibody production by aged mice

PMCID: PMC2187002  PMID: 6343547

Abstract

We have previously shown that old mice produce more hapten-augmentable plaque-forming cells (PFC) than do young animals, suggesting a greater auto-antiidiotype antibody (auto anti-Id) component in their immune response. In the present studies this is confirmed serologically. The marked auto-anti-Id response of aged mice can be transferred to lethally irradiated young recipients with spleen but not bone marrow cells from old donors, suggesting that it is an intrinsic property of their peripheral B cell population and that the distribution of Id arising from the bone marrow of old and young mice is similar. In contrast with young mice the auto-anti-Id response of old animals is relatively T cell-independent and old donors do not show an increase in their ability to transfer an auto-anti-Id response after priming with TNP-F. These observations suggest that old mice behave as if already primed for auto-anti-Id production. Irradiated mice reconstituted with bone marrow cells from either young or old donors together with splenic T cells from old donors generate a relatively large auto-anti-Id response, whereas mice reconstituted with bone marrow from either young or old donors together with splenic T cells from young donors produce few hapten-augmentable PFC. It is suggested that differences in Id expression and auto-anti-Id production are the consequences of the interaction of Id (and anti-Id) arising from the marrow with anti-Id (and Id) present in the peripheral T cell population which serves as a repository of information about shifts in Id distribution, resulting from lifelong interactions with environmental and self-antigens.

Full Text

The Full Text of this article is available as a PDF (852.5 KB).

Selected References

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

  1. Bankert R. B., Mazzaferro D., Mayers G. L. Hybridomas producing hemolytic plaques used to study the relationship between monoclonal antibody affinity and the efficiency of plaque inhibition with increasing concentrations of antigen. Hybridoma. 1981;1(1):47–58. doi: 10.1089/hyb.1.1981.1.47. [DOI] [PubMed] [Google Scholar]
  2. Brooks K. H., Feldbush T. L. Generation of antibody-mediated regulation during in vitro clonal expansion of memory B lymphocytes. J Immunol. 1981 Sep;127(3):963–967. [PubMed] [Google Scholar]
  3. Callard R. E., Basten A. Immune function in aged mice. I. T-cell responsiveness using phytohaemagglutinin as a functional probe. Cell Immunol. 1977 Jun 1;31(1):13–25. doi: 10.1016/0008-8749(77)90002-8. [DOI] [PubMed] [Google Scholar]
  4. Claflin J. L., Lieberman R., Davie J. M. Clonal nature of the immune response to phosphorylcholine. II. Idiotypic specificity and binding characteristics of anti-phosphorylcholine antibodies. J Immunol. 1974 May;112(5):1747–1756. [PubMed] [Google Scholar]
  5. Goidl E. A., Innes J. B., Weksler M. E. Immunological studies of aging. II. Loss of IgG and high avidity plaque-forming cells and increased suppressor cell activity in aging mice. J Exp Med. 1976 Oct 1;144(4):1037–1048. doi: 10.1084/jem.144.4.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goidl E. A., Michelis M. A., Siskind G. W., Weksler M. E. Effect of age on the induction of autoantibodies. Clin Exp Immunol. 1981 Apr;44(1):24–30. [PMC free article] [PubMed] [Google Scholar]
  7. Goidl E. A., Schrater A. F., Siskind G. W., Thorbecke G. J. Production of auto-anti-idiotypic antibody during the normal immune response to TNP-Ficoll. II. Hapten-reversible inhibition of anti-TNP plaque-forming cells by immune serum as an assay for auto-anti-idiotypic antibody. J Exp Med. 1979 Jul 1;150(1):154–165. doi: 10.1084/jem.150.1.154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goidl E. A., Schrater A. F., Thorbecke G. H., Siskind G. W. Production of auto-anti-idiotypic antibody during the normal immune response. IV. Studies of the primary and secondary responses to thymus-dependent and -independent antigens. Eur J Immunol. 1980 Nov;10(11):810–814. doi: 10.1002/eji.1830101103. [DOI] [PubMed] [Google Scholar]
  9. Goidl E. A., Thorbecke G. J., Weksler M. E., Siskind G. W. Production of auto-anti-idiotypic antibody during the normal immune response: changes in the auto-anti-idiotypic antibody response and the idiotype repertoire associated with aging. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6788–6792. doi: 10.1073/pnas.77.11.6788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hallgren H. M., Buckley C. E., 3rd, Gilbertsen V. A., Yunis E. J. Lymphocyte phytohemagglutinin responsiveness, immunoglobulins and autoantibodies in aging humans. J Immunol. 1973 Oct;111(4):1101–1107. [PubMed] [Google Scholar]
  11. Harrison D. E., Astle C. M., Delaittre J. A. Loss of proliferative capacity in immunohemopoietic stem cells caused by serial transplantation rather than aging. J Exp Med. 1978 May 1;147(5):1526–1531. doi: 10.1084/jem.147.5.1526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Harrison D. E., Astle C. M., Doubleday J. W. Cell lines from old immunodeficient donors give normal responses in young recipients. J Immunol. 1977 Apr;118(4):1223–1227. [PubMed] [Google Scholar]
  13. Hori Y., Perkins E. H., Halsall M. K. Decline in phytohemagglutinin responsiveness of spleen cells from aging mice. Proc Soc Exp Biol Med. 1973 Oct 1;144(1):48–53. doi: 10.3181/00379727-144-37524. [DOI] [PubMed] [Google Scholar]
  14. Hosono M., Fujiwara M. Studies on the resistance to tolerance induction against human IgG in DDD mice. III. Development of the resistance with age and cellular events. Cell Immunol. 1979 May;44(2):262–269. doi: 10.1016/0008-8749(79)90004-2. [DOI] [PubMed] [Google Scholar]
  15. JERNE N. K., NORDIN A. A. Plaque formation in agar by single antibody-producing cells. Science. 1963 Apr 26;140(3565):405–405. [PubMed] [Google Scholar]
  16. Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
  17. Kelsoe G., Cerny J. Reciprocal expansions of idiotypic and anti-idiotypic clones following antigen stimulation. Nature. 1979 May 24;279(5711):333–334. doi: 10.1038/279333a0. [DOI] [PubMed] [Google Scholar]
  18. Klinman N. R. Antibody-specific immunoregulation and the immunodeficiency of aging. J Exp Med. 1981 Aug 1;154(2):547–551. doi: 10.1084/jem.154.2.547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mackay I. R. Ageing and immunological function in man. Gerontologia. 1972;18(5-6):285–304. doi: 10.1159/000211941. [DOI] [PubMed] [Google Scholar]
  20. Makinodan T., Perkins E. H., Chen M. G. Immunologicc activity of the aged. Adv Gerontol Res. 1971;3:171–198. [PubMed] [Google Scholar]
  21. McIntosh K. R., Segre D. B- and T-cell tolerance induction in young-adult and old mice. Cell Immunol. 1976 Dec;27(2):230–239. doi: 10.1016/0008-8749(76)90231-8. [DOI] [PubMed] [Google Scholar]
  22. Rittenberg M. B., Pratt K. L. Antitrinitrophenyl (TNP) plaque assay. Primary response of Balb/c mice to soluble and particulate immunogen. Proc Soc Exp Biol Med. 1969 Nov;132(2):575–581. doi: 10.3181/00379727-132-34264. [DOI] [PubMed] [Google Scholar]
  23. Schrater A. F., Goidl E. A., Thorbecke G. J., Siskind G. W. Production of auto-anti-idiotypic antibody during the normal immune response to TNP-ficoll. I. Occurrence in AKR/J and BALB/c mice of hapten-augmentable, anti-TNP plaque-forming cells and their accelerated appearance in recipients of immune spleen cells. J Exp Med. 1979 Jul 1;150(1):138–153. doi: 10.1084/jem.150.1.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schrater A. F., Goidl E. A., Thorbecke G. J., Siskind G. W. Production of auto-anti-idiotypic antibody during the normal immune response to TNP-ficoll. III. Absence in nu/nu mice: evidence for T-cell dependence of the anti-idiotypic-antibody response. J Exp Med. 1979 Oct 1;150(4):808–817. doi: 10.1084/jem.150.4.808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Szewczuk M. R., Campbell R. J. Loss of immune competence with age may be due to auto-anti-idiotypic antibody regulation. Nature. 1980 Jul 10;286(5769):164–166. doi: 10.1038/286164a0. [DOI] [PubMed] [Google Scholar]
  26. Walters C. S., Claman H. N. Age-related changes in cell-mediated immunity in BALB/C mice. J Immunol. 1975 Nov;115(5):1438–1443. [PubMed] [Google Scholar]
  27. Werblin T. P., Kim Y. T., Quagliata F., Siskind G. W. Studies on the control of antibody synthesis. 3. Changes in heterogeneity of antibody affinity during the course of the immune response. Immunology. 1973 Mar;24(3):477–492. [PMC free article] [PubMed] [Google Scholar]
  28. Woodland R. T., Zimmerman D. M., Schrater A. F. Anti-hapten antibody in primary immune antiserum can specifically inhibit antibody-secreting cells. J Immunol. 1982 Nov;129(5):2009–2015. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES