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. 1980 Jul 1;152(1):138–150. doi: 10.1084/jem.152.1.138

Activation of murine B lymphocytes by anti-immunoglobulin is an inductive signal leading to immunoglobulin secretion

PMCID: PMC2185896  PMID: 6967509

Abstract

Cultures of isolated mouse splenic B lymphocytes activated by the divalent F(ab')2 fragment of purified rabbit anti-mouse Fab or class- specific anti-mouse IgM antibodies can be driven on to high rate Ig secretion by the addition of the supernatant fluid of a 24-h culture of concanavalin A-activated spleen cells (SN). The polyclonal antibody response to anti-Ig pus SN is comparable in magnitude with the lipopolysaccharide response as measured in a reverse plaque assay. The addition of SN can be delayed for 24 h after addition of anti-Ig without changing the kinetics of the response. Addition at 48 h delays the response by 24 h. The response to F(ab')2 anti-Fab plus SN is sensitive to Fc-dependent inhibition because intact anti-Fab antibodies inhibit strongly at relatively low concentrations. The monovalent Fab' fragment fails to induce Ig secretion, indicating that cross-linkage of surface immunoglobulin is required. Although the production of active SN is T cell dependent, the response to anti-Ig plus SN is T independent. These findings are interpreted as a polyclonal model of a thymus-dependent antibody response. X

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Selected References

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

  1. Alexander E. L., Sanders S. K. F(ab')2 reagents are not required if goat, rather than rabbit, antibodies are used to detect human surface immunoglobulin. J Immunol. 1977 Sep;119(3):1084–1088. [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. Chan P. L., Sinclair N. R. Regulation of the immune response. VI. Inability of F(ab') 2 antibody to terminate established immune responses and its ability to interfere with IgG antibody-mediated immunosuppression. Immunology. 1973 Feb;24(2):289–301. [PMC free article] [PubMed] [Google Scholar]
  4. Cowing C., Schwartz B. D., Dickler H. B. Macrophage Ia antigens. I. macrophage populations differ in their expression of Ia antigens. J Immunol. 1978 Feb;120(2):378–384. [PubMed] [Google Scholar]
  5. Dutton R. W. Separate signals for the initiation of proliferation and differentiation in the b cell response to antigen. Transplant Rev. 1975;23:66–77. doi: 10.1111/j.1600-065x.1975.tb00149.x. [DOI] [PubMed] [Google Scholar]
  6. Fanger M. W., Hart D. A., Wells J. V., Nisonoff A. Requirement for cross-linkage in the stimulation of transformation of rabbit peripheral lymphocytes by antiglobulin reagents. J Immunol. 1970 Dec;105(6):1484–1492. [PubMed] [Google Scholar]
  7. Hünig T. H., Schimpl A., Wecker E. Mechanism of T-cell help in the immune response to soluble protein antigens II. Reconstitution of primary and secondary in vitro immune responses to dinitrophenyl-carrier conjugates by T-cell-replacing factor. J Exp Med. 1977 May 1;145(5):1228–1236. doi: 10.1084/jem.145.5.1228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hünig T., Schimpl A., Wecker E. Autoradiographic studies on the proliferation of antibody-producing cells in vitro. J Exp Med. 1974 Mar 1;139(3):754–760. doi: 10.1084/jem.139.3.754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kearney J. F., Klein J., Bockman D. E., Cooper M. D., Lawton A. R. B cell differentiation induced by lipopolysaccharide. V. Suppression of plasma cell maturation by anti-mu: mode of action and characteristics of suppressed cells. J Immunol. 1978 Jan;120(1):158–166. [PubMed] [Google Scholar]
  10. Kettman J. R., Cambier J. C., Uhr J. W., Ligler F., Vitetta E. S. The role of receptor IgM and IgD in determining triggering and induction of tolerance in murine B cells. Immunol Rev. 1979;43:69–95. doi: 10.1111/j.1600-065x.1979.tb00418.x. [DOI] [PubMed] [Google Scholar]
  11. Kishimoto T., Miyake T., Nishizawa Y., Watanabe T., Yamamura Y. Triggering mechanism of B lymphocytes. I. Effect of anti-immunoglobulin and enhancing soluble factor on differentiation and proliferation of B cells. J Immunol. 1975 Nov;115(5):1179–1184. [PubMed] [Google Scholar]
  12. Lake P., Clark E. A., Khorshidi M., Sunshine G. H. Production and characterization of cytotoxic Thy-1 antibody-secreting hybrid cell lines. Detection of T cell subsets. Eur J Immunol. 1979 Nov;9(11):875–886. doi: 10.1002/eji.1830091109. [DOI] [PubMed] [Google Scholar]
  13. Mosier D. E., Zitron I. M., Mond J. J., Ahmed A., Scher I., Paul W. E. Surface immunoglobulin D as a functional receptor for a subclass of B lymphocytes. Immunol Rev. 1977;37:89–104. doi: 10.1111/j.1600-065x.1977.tb00246.x. [DOI] [PubMed] [Google Scholar]
  14. Parker D. C., Fothergill J. J., Wadsworth D. C. B lymphocyte activation by insoluble anti-immunoglobulin: induction of immunoglobulin secretion by a T cell-dependent soluble factor. J Immunol. 1979 Aug;123(2):931–941. [PubMed] [Google Scholar]
  15. Parker D. C. Stimulation of mouse lymphocytes by insoluble anti-mouse immunoglobulin. Nature. 1975 Nov 27;258(5533):361–363. doi: 10.1038/258361a0. [DOI] [PubMed] [Google Scholar]
  16. SELL S., GELL P. G. STUDIES ON RABBIT LYMPHOCYTES IN VITRO. I. STIMULATION OF BLAST TRANSFORMATION WITH AN ANTIALLOTYPE SERUM. J Exp Med. 1965 Aug 1;122:423–440. doi: 10.1084/jem.122.2.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Scott D. W., Venkataraman M., Jandinski J. J. Multiple pathways of B lymphocyte tolerance. Immunol Rev. 1979;43:241–280. doi: 10.1111/j.1600-065x.1979.tb00424.x. [DOI] [PubMed] [Google Scholar]
  18. Scribner D. J., Weiner H. L., Moorhead J. W. Anti-immunoglobulin stimulation of murine lymphocytes. V. Age-related decline in Fc receptor-mediated immunoregulation. J Immunol. 1978 Jul;121(1):377–382. [PubMed] [Google Scholar]
  19. Sell S., Rowe D. S., Gell P. G. Studies on rabbit lymphocytes in vitro. 3. Proteins, RNA, and DNA synthesis by lymphocyte cultures after stimulation with phytohaemagglutinin, with staphylococcal filtrate, with antiallotype serum, and with heterologous antiserum to rabbit whole serum. J Exp Med. 1965 Oct 1;122(4):823–839. doi: 10.1084/jem.122.4.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sidman C. L., Unanue E. R. Control of proliferation and differentiation in B lymphocytes by anti-Ig antibodies and a serum-derived cofactor. Proc Natl Acad Sci U S A. 1978 May;75(5):2401–2405. doi: 10.1073/pnas.75.5.2401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sidman C. L., Unanue E. R. Proliferative response to anti-IgM antibodies of various B lymphocyte subpopulations isolated by cell sorting. J Immunol. 1978 Dec;121(6):2129–2136. [PubMed] [Google Scholar]
  22. Sidman C. L., Unanue E. R. Requirements for mitogenic stimulation of murine B cells by soluble anti-IgM antibodies. J Immunol. 1979 Feb;122(2):406–413. [PubMed] [Google Scholar]
  23. Sieckmann D. G., Asofsky R., Mosier D. E., Zitron I. M., Paul W. E. Activation of mouse lymphocytes by anti-immunoglobulin. I. Parameters of the proliferative response. J Exp Med. 1978 Mar 1;147(3):814–829. doi: 10.1084/jem.147.3.814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sieckmann D. G., Scher I., Asofsky R., Mosier D. E., Paul W. E. Activation of mouse lymphocytes by anti-immunoglobulin. II. A thymus-independent response by a mature subset of B lymphocytes. J Exp Med. 1978 Dec 1;148(6):1628–1643. doi: 10.1084/jem.148.6.1628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Vitetta E. S., Uhr J. W. Immunoglobulin-receptors revisited. Science. 1975 Sep 19;189(4207):964–969. doi: 10.1126/science.1083069. [DOI] [PubMed] [Google Scholar]
  26. Weiner H. L., Moorhead J. W., Yamaga K., Kubo R. T. Anti-immunoglobulin stimulation of murine lymphocytes. II. Identification of cell surface target molecules and requirements for cross-linkage. J Immunol. 1976 Nov;117(5 Pt 1):1527–1531. [PubMed] [Google Scholar]

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