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. 1980 Mar 1;151(3):667–680. doi: 10.1084/jem.151.3.667

Feedback suppression of the immune response in vitro. I. Activity of antigen-stimulated B cells

PMCID: PMC2185815  PMID: 6444663

Abstract

Feedback regulation of the primary humoral immune response to sheep erythrocytes (SRBC) was studied in vitro. Whole spleen cells or spleen cell subpopulations were incubated with antigen for 4 d under Mishell- Dutton conditions (education) and the surviving cells tested for regulatory activity in fresh anti-SRBC spleen cell cultures assayed by measuring plaque-forming cells on day 4. The data indicate that (a) whole spleen cells educated with SRBC exert potent antigen-specific suppression in the assay culture, (b) surface Ig- (sIg-) cells (T cells) prepared by either nylon-wool separation or fractionation on rabbit anti-mouse-Ig-coated polystyrene Petri dishes failed to generate suppressive activity when educated alone, in 2-mercaptoethanol, or in the presence of additional macrophages, (c) surface Ig (sIg+) (B) cells educated alone also failed to generate suppressor cells, and (d) mixing sIg- (T) and sIg+, Lyt 123- (B) cells reconstituted the ability to induce suppressor cells under these conditions. The antigen-primed cell actually required to transfer suppression was also characterized by separating cells using anti-Ig coated dishes, by fluorescence-activated cell sorting and by anti-Lyt treatment. All these methods clearly identified sIg+ (B) and not sIg+ (T) cells as the important educated cells. It is concluded that under our conditions, T cell-dependent B cells triggered by antigen during primary in vitro cultures cause potent specific feedback suppression of humoral responses. Possible mechanisms for this suppression, including antigen blockade or anti- idiotypic responses, are discussed.

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Selected References

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

  1. Cantor H., Boyse E. A. Regulation of cellular and humoral immune responses by T-cell subclasses. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):23–32. doi: 10.1101/sqb.1977.041.01.006. [DOI] [PubMed] [Google Scholar]
  2. Cantor H., Hugenberger J., McVay-Boudreau L., Eardley D. D., Kemp J., Shen F. W., Gershon R. K. Immunoregulatory circuits among T-cell sets. Identification of a subpopulation of T-helper cells that induces feedback inhibition. J Exp Med. 1978 Oct 1;148(4):871–877. doi: 10.1084/jem.148.4.871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cantor H., McVay-Boudreau L., Hugenberger J., Naidorf K., Shen F. W., Gershon R. K. Immunoregulatory circuits among T-cell sets. II. Physiologic role of feedback inhibition in vivo: absence in NZB mice. J Exp Med. 1978 Apr 1;147(4):1116–1125. doi: 10.1084/jem.147.4.1116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Eardley D. D., Gershon R. K. Induction of specific suppressor T cells in vitro. J Immunol. 1976 Jul;117(1):313–318. [PubMed] [Google Scholar]
  5. Eardley D. D., Hugenberger J., McVay-Boudreau L., Shen F. W., Gershon R. K., Cantor H. Immunoregulatory circuits among T-cell sets. I. T-helper cells induce other T-cell sets to exert feedback inhibition. J Exp Med. 1978 Apr 1;147(4):1106–1115. doi: 10.1084/jem.147.4.1106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eardley D. D., Kemp J., Shen F. W., Cantor H., Gershon R. K. Immunoregulatory circuits among T cell sets: effect of mode of immunization on determining which Lyl T cell sets will be activated. J Immunol. 1979 May;122(5):1663–1665. [PubMed] [Google Scholar]
  7. Eichmann K. Expression and function of idiotypes of lymphocytes. Adv Immunol. 1978;26:195–254. doi: 10.1016/s0065-2776(08)60231-x. [DOI] [PubMed] [Google Scholar]
  8. Fitch F. W. Selective suppression of immune responses. Regulation of antibody formation and cell-mediated immunity by antibody. Prog Allergy. 1975;19:195–244. [PubMed] [Google Scholar]
  9. Germain R. N., Ju S. T., Kipps T. J., Benacerraf B., Dorf M. E. Shared idiotypic determinants on antibodies and T-cell-derived suppressor factor specific for the random terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10. J Exp Med. 1979 Mar 1;149(3):613–622. doi: 10.1084/jem.149.3.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Germain R. N., Thèze J., Kapp J. A., Benacerraf B. Antigen-specific T-cell-mediated suppression. I. Induction of L-glutamic acid60-L-alanine30-L-tyrosine10 specific suppressor T cells in vitro requires both antigen-specific T-cell-suppressor factor and antigen. J Exp Med. 1978 Jan 1;147(1):123–136. doi: 10.1084/jem.147.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gershon R. K. T cell control of antibody production. Contemp Top Immunobiol. 1974;3:1–40. doi: 10.1007/978-1-4684-3045-5_1. [DOI] [PubMed] [Google Scholar]
  12. Gill H. K., Liew F. Y. Regulation of delayed-type hypersensitivity IV. Antigen-specific suppressor cells for delayed-type hypersensitivity induced by lipopolysaccharide and sheep erythrocytes in mice. Eur J Immunol. 1979 Feb;9(2):101–106. doi: 10.1002/eji.1830090202. [DOI] [PubMed] [Google Scholar]
  13. Ishizaka K., Adachi T. Generation of specific helper cells and suppressor cells in vitro for the IgE and IgG antibody responses. J Immunol. 1976 Jul;117(1):40–47. [PubMed] [Google Scholar]
  14. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  15. Kapp J. A., Pierce C. W., De la Croix F., Benacerraf B. Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). J Immunol. 1976 Feb;116(2):305–309. [PubMed] [Google Scholar]
  16. Mage M. G., McHugh L. L., Rothstein T. L. Mouse lymphocytes with and without surface immunoglobulin: preparative scale separation in polystyrene tissue culture dishes coated with specifically purified anti-immunoglobulin. J Immunol Methods. 1977;15(1):47–56. doi: 10.1016/0022-1759(77)90016-3. [DOI] [PubMed] [Google Scholar]
  17. McDougal J. S., Shen F. W., Elster P. Generation of T helper cells in vitro. V. Antigen-specific Ly1+ T cells mediate the helper effect and induce feedback suppression. J Immunol. 1979 Feb;122(2):437–442. [PubMed] [Google Scholar]
  18. Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Morris A., Möller G. Regulation of cellular antibody synthesis effect of adoptively transferred antibody-producing spleen cells on cellular antibody synthesis. J Immunol. 1968 Sep;101(3):439–445. [PubMed] [Google Scholar]
  20. Neta R., Salvin S. B. T and B lymphocytes in the regulation of delayed hypersensitivity. J Immunol. 1976 Nov;117(5 PT2):2014–2020. [PubMed] [Google Scholar]
  21. Pierce C. W. Immune responses in vitro. II. Suppression of the immune response in vitro by specific antibody. J Exp Med. 1969 Aug 1;130(2):365–379. doi: 10.1084/jem.130.2.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pierce C. W., Johnson B. M., Gershon H. E., Asofsky R. Immune responses in vitro. 3. Development of primary gamma-M, gamma-G, and gamma-A plaque-forming cell responses in mouse spleen cell cultures stimulated with heterologous erythrocytes. J Exp Med. 1971 Aug 1;134(2):395–416. doi: 10.1084/jem.134.2.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pierce C. W., Kapp J. A. Regulation of immune responses by suppressor T cells. Tohoku J Exp Med. 1976;5:91–143. [PubMed] [Google Scholar]
  24. Pierres M., Germain R. N. Antigen-specific T cell-mediated suppression. IV. Role of macrophages in generation of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT)-specific suppressor T cells in responder mouse strains. J Immunol. 1978 Oct;121(4):1306–1314. [PubMed] [Google Scholar]
  25. Tada T., Taniguchi M., Takemori T. Properties of primed suppressor T cells and their products. Transplant Rev. 1975;26:106–129. doi: 10.1111/j.1600-065x.1975.tb00177.x. [DOI] [PubMed] [Google Scholar]
  26. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zembala M., Asherson G. L., Noworolski J., Mayhew B. Contact sensitivity to picryl chloride: the occurrence of B suppressor cells in the lymph nodes and spleen of immunized mice. Cell Immunol. 1976 Aug;25(2):266–278. doi: 10.1016/0008-8749(76)90117-9. [DOI] [PubMed] [Google Scholar]
  28. Zubler R. H., Benacerraf B., Germain R. N. Feedback suppression of the immune response in vitro. II. IgVH-restricted antibody-dependent suppression. J Exp Med. 1980 Mar 1;151(3):681–694. doi: 10.1084/jem.151.3.681. [DOI] [PMC free article] [PubMed] [Google Scholar]

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