Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1975 Oct 1;142(4):814–826. doi: 10.1084/jem.142.4.814

Inhibition of lymphocyte mitogenesis by immobilized antigen-antibody complexes

PMCID: PMC2189949  PMID: 1185105

Abstract

Mouse spleen cells, cultured on surfaces coated with antigen-antibody complexes, are inhibited from responding to the B-cell mitogens, lipopolysaccharide, lipid A, Pneumococcal polysaccharide SIII, and poly I:C. The response to the T-cell mitogen, concanavalin A, is also substantially inhibited by immobilized antigen-antibody complexes, but specific inhibition of the response to phytohemagglutinin is minimal. Control experiments showed that immobilized complexes prepared from IgG F(ab')2 fragments and IgA antibodies (both of which fail to bind to Fc receptors when complexed to antigen) did not show significant inhibitory activity when compared with the inhibition observed with complexes prepared from whole IgG. Suspensions of antigen-antibody complexes prepared from the same antigen and intact IgG antibody did not inhibit mitogenesis. None of the mitogens used could be demonstrated to compete with the binding of aggregated immunoglobulin to the B-cell Fc receptor. It appears that the interaction of Fc receptor-bearing lymphocytes and/or macrophages with immobilized complexes prevents lymphocyte activation by mitogens. It is suggested that the mechanism(s) involved may be relevant to antibody feedback control of the humoral immune response.

Full Text

The Full Text of this article is available as a PDF (687.5 KB).

Selected References

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

  1. Anderson C. L., Grey H. M. Receptors for aggregated IgG on mouse lymphocytes: their presence on thymocytes, thymus-derived, and bone marrow-derived lymphocytes. J Exp Med. 1974 May 1;139(5):1175–1188. doi: 10.1084/jem.139.5.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andersson J., Bullock W. W., Melchers F. Inhibition of mitogenic stimulation of mouse lymphocytes by anti-mouse immunoglobulin antibodies. I. Mode of action. Eur J Immunol. 1974 Nov;4(11):715–722. doi: 10.1002/eji.1830041103. [DOI] [PubMed] [Google Scholar]
  3. Andersson J., Edelman G. M., Möller G., Sjöberg O. Activation of B lymphocytes by locally concentrated concanavalin A. Eur J Immunol. 1972 Jun;2(3):233–235. doi: 10.1002/eji.1830020307. [DOI] [PubMed] [Google Scholar]
  4. Andersson J., Melchers F., Galanos C., Lüderitz O. The mitogenic effect of lipopolysaccharide on bone marrow-derived mouse lymphocytes. Lipid A as the mitogenic part of the molecule. J Exp Med. 1973 Apr 1;137(4):943–953. doi: 10.1084/jem.137.4.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Basten A., Miller J. F., Sprent J., Pye J. A receptor for antibody on B lymphocytes. I. Method of detection and functional significance. J Exp Med. 1972 Mar 1;135(3):610–626. doi: 10.1084/jem.135.3.610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Basten A., Warner N. L., Mandel T. A receptor for antibody on B lymphocytes. II. Immunochemical and electron microscopy characteristics. J Exp Med. 1972 Mar 1;135(3):627–642. doi: 10.1084/jem.135.3.627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Berken A., Benacerraf B. Properties of antibodies cytophilic for macrophages. J Exp Med. 1966 Jan 1;123(1):119–144. doi: 10.1084/jem.123.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bloch-Shtacher N., Hirschhorn K., Uhr J. W. The response of lymphocytes from non-immunized humans to antigen-antibody complexes. Clin Exp Immunol. 1968 Nov;3(9):889–899. [PMC free article] [PubMed] [Google Scholar]
  9. Bona C., Anteunis A., Robineaux R., Astesano A. Transfer of antigenic macromolecules from macrophages to lymphocytes. I. Autoradiographic and quantitative study of ( 14 C)endotoxin and ( 125 I)haemocyanin transfer. Immunology. 1972 Dec;23(6):799–816. [PMC free article] [PubMed] [Google Scholar]
  10. Cerottini J. C., Brunner K. T. Cell-mediated cytotoxicity, allograft rejection, and tumor immunity. Adv Immunol. 1974;18:67–132. doi: 10.1016/s0065-2776(08)60308-9. [DOI] [PubMed] [Google Scholar]
  11. Coutinho A., Möller G., Anderson J., Bullock W. W. In vitro activation of mouse lymphocytes in serum-free medium: effect of T and B cell mitogens on proliferation and antibody synthesis. Eur J Immunol. 1973 May;3(5):299–306. doi: 10.1002/eji.1830030509. [DOI] [PubMed] [Google Scholar]
  12. Dickler H. B., Kunkel H. G. Interaction of aggregated -globulin with B lymphocytes. J Exp Med. 1972 Jul 1;136(1):191–196. doi: 10.1084/jem.136.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dickler H. B., Sachs D. H. Evidence for identity or close association of the Fc receptor of B lymphocytes and alloantigens determined by the Ir region of the H-2 complex. J Exp Med. 1974 Sep 1;140(3):779–796. doi: 10.1084/jem.140.3.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Feldmann M., Greaves M. F., Parker D. C., Rittenberg M. B. Direct triggering of B lymphocytes by insolubilized antigen. Eur J Immunol. 1974 Sep;4(9):591–597. doi: 10.1002/eji.1830040903. [DOI] [PubMed] [Google Scholar]
  15. Galanos C., Rietschel E. T., Lüderitz O., Westphal O., Kim Y. B., Watson D. W. Biological activities of lipid A complexed with bovine-serum albumin. Eur J Biochem. 1972 Dec 4;31(2):230–233. doi: 10.1111/j.1432-1033.1972.tb02524.x. [DOI] [PubMed] [Google Scholar]
  16. Greaves M. F., Bauminger S. Activation of T and B lymphocytes by insoluble phytomitogens. Nat New Biol. 1972 Jan 19;235(55):67–70. doi: 10.1038/newbio235067a0. [DOI] [PubMed] [Google Scholar]
  17. Möller G., Coutinho A. Role of C'3 and Fc receptors in B-lymphocyte activation. J Exp Med. 1975 Mar 1;141(3):647–663. doi: 10.1084/jem.141.3.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Möller G. Induction of DNA synthesis in normal human lymphocyte cultures by antigen-antibody complexes. Clin Exp Immunol. 1969 Jan;4(1):65–82. [PMC free article] [PubMed] [Google Scholar]
  19. Nicholas R., Sinclair S. C. Regulation of the immune response. I. Reduction in ability of specific antibody to inhibit long-lasting IgG immunological priming after removal of the Fc fragment. J Exp Med. 1969 Jun 1;129(6):1183–1201. doi: 10.1084/jem.129.6.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Peters J. H. Contact cooperation in stimulated lymphocytes. I. Influence of cell contact on unspecifically stimulated lymphocytes. Exp Cell Res. 1972 Sep;74(1):179–186. doi: 10.1016/0014-4827(72)90495-8. [DOI] [PubMed] [Google Scholar]
  21. Robbins J. B., Haimovich J., Sela M. Purification of antibodies with immunoadsorbents prepared using bromoacetyl cellulose. Immunochemistry. 1967 Jan;4(1):11–22. doi: 10.1016/0019-2791(67)90192-9. [DOI] [PubMed] [Google Scholar]
  22. Sachs D. H., Dickler H. B. The possible role of i region determined cell surface molecules in the regulation of immune responses. Transplant Rev. 1975;23:159–175. doi: 10.1111/j.1600-065x.1975.tb00156.x. [DOI] [PubMed] [Google Scholar]
  23. Uhr J. W., Möller G. Regulatory effect of antibody on the immune response. Adv Immunol. 1968;8:81–127. doi: 10.1016/s0065-2776(08)60465-4. [DOI] [PubMed] [Google Scholar]
  24. Watson J. The influence of intracellular levels of cyclic nucleotides on cell proliferation and the induction of antibody synthesis. J Exp Med. 1975 Jan 1;141(1):97–111. doi: 10.1084/jem.141.1.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yoshida T. O., Andersson B. Evidence for a receptor recognizing antigen complexed immunoglobulin on the surface of activated mouse thymus lymphocytes. Scand J Immunol. 1972;1(4):401–408. doi: 10.1111/j.1365-3083.1972.tb03306.x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES