Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1977 Jun 1;145(6):1436–1448. doi: 10.1084/jem.145.6.1436

The specificity of T-cell helper factor in man

RS Geha, F Mudawwar, E Schneeberger
PMCID: PMC2180692  PMID: 301172

Abstract

Supernates of human T cells stimulated with TT antigen contain a factor that induces mitogenesis and immunoglobulin synthesis in autologous as well as allogeneic B cells. A fraction of the IgG produced has specificity against TT. The T-cell-derived LMF-TT eluted after albumin on Sephadex G 200 and did not contain immunoglobulin heavy chain determinants. LMF-TT was active on B cells from TT immune as well as TT- nonimmune individuals but in the latter instance the IgG secreted had no specificity against TT. B cells incubated with LMF-TT in the presence of a second antigen (DT) made IgG with specifity to that antigen provided the B-cell donor was immune to that second antigen. LMF-TT-containing supernates were depleted of TT antigen by Sephadex G 200 chromatography followed by passage over anti-TT immunosorbent columns. The antigen-free supernates were able to induce mitogenesis and IgG synthesis in B cells but the IgG produced failed to exhibit specificity against TT unless the TT antigen was readded to the B-cell cultures. The optimal concentration of LMF-TT (50 percent) inducing B-cell mitogenesis was different from the optimal concentration (20 percent) causing IgG synthesis by B cells. At low LMF concentrations (less than or equal 10 percent) addition of a second antigen to which the cell donor was immune caused an increase in the degree of B-cell mitogenesis. Submitogenic concentrations of LMF-TT (less than or equal to 5 percent) were still capable of inducingimmunoglobulin synthesis in B cells At these low concentrations of LMF-TT the proportion of anti-TT IgG over total IgG increased sharply. B cells from TT immune donors were separated on TT immunosorbent columns. Cells that bound to the column were more sensitive to the mitogenic and IgG synthetic effects of LMF-TT than unfractionated B cells. Thus, LMF is a nonspecific human T-cell helper factor which behaves like a polyclonal B-cell activator. However, in the presence of specific antigen (TT) the antigen-specific B cell is preferentially triggered by LMF. The experimental design of the present study does not rule out the additional presence of an antigen-specific helper factor in the supernates of TT-stimulated human T cells.

Full Text

The Full Text of this article is available as a PDF (992.6 KB).

Selected References

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

  1. Andersson J., Melchers F. Maturation of mitogen-activated bone marrow-derived lymphocytes in the absence of proliferation. Eur J Immunol. 1974 Aug;4(8):533–539. doi: 10.1002/eji.1830040803. [DOI] [PubMed] [Google Scholar]
  2. Armerding D., Katz D. H. Activation of T and B lymphocytes in vitro. II. Biological and biochemical properties of an allogeneic effect factor (AEF) active in triggering specific B lymphocytes. J Exp Med. 1974 Jul 1;140(1):19–37. doi: 10.1084/jem.140.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Coutinho A., Möller G. Editorial: Immune activation of B cells: evidence for 'one nonspecific triggering signal' not delivered by the Ig receptors. Scand J Immunol. 1974;3(2):133–146. [PubMed] [Google Scholar]
  4. Feldmann M., Basten A. Cell interactions in the immune response in vitro. IV. Comparison of the effects of antigen-specific and allogeneic thymus-derived cell factors. J Exp Med. 1972 Oct 1;136(4):722–736. doi: 10.1084/jem.136.4.722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Friedman S. M., Breard J. M., Chess L. Triggering of human peripheral blood B cells: polyclonal induction and modulation of an in vitro PFC response. J Immunol. 1976 Nov;117(5 PT2):2021–2028. [PubMed] [Google Scholar]
  6. Geha R. S., Rosen F. S., Merler E. Identification and characterization of subpopulations of lymphocytes in human peripheral blood after fractionation on discontinuous gradients of albumin. The cellular defect in X-linked agammaglobulinemia. J Clin Invest. 1973 Jul;52(7):1726–1734. doi: 10.1172/JCI107354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Geha R. S., Schneeberger E., Rosen F. S., Merler E. Interaction of human thymus-derived and non-thymus-derived lymphocytes in vitro. Induction of proliferation and antibody synthesis in B lymphocytes by a soluble factor released from antigen-stimulated T lymphocytes. J Exp Med. 1973 Nov 1;138(5):1230–1247. doi: 10.1084/jem.138.5.1230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gold E. R., Fudenberg H. H. Chromic chloride: a coupling reagent for passive hemagglutination reactions. J Immunol. 1967 Nov;99(5):859–866. [PubMed] [Google Scholar]
  9. Gronowicz E., Coutinho A. Functional analysis of B cell heterogeneity. Transplant Rev. 1975;24:3–40. doi: 10.1111/j.1600-065x.1975.tb00164.x. [DOI] [PubMed] [Google Scholar]
  10. Harwell L., Kappler J. W., Marrack P. Antigen-specific and nonspecific mediators of T cell/B cell cooperation. III. Characterization of the nonspecific mediator(s) from different sources. J Immunol. 1976 May;116(5):1379–1384. [PubMed] [Google Scholar]
  11. Hunter P., Kettman J. R. Mode of action of a supernatant activity from T-cell cultures that nonspecifically stimulates the humoral immune response. Proc Natl Acad Sci U S A. 1974 Feb;71(2):512–516. doi: 10.1073/pnas.71.2.512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. LEVINE L., WYMAN L. THE FLOCCULATION TEST AND THE LAW OF MASS ACTION. J Immunol. 1965 Apr;94:586–591. [PubMed] [Google Scholar]
  13. Marrack P. C., Kappler J. W. Antigen-specific and nonspecific mediators of T cell/B cell cooperation. I. Evidence for their production by different T cells. J Immunol. 1975 Mar;114(3):1116–1125. [PubMed] [Google Scholar]
  14. Munro A. J., Taussig M. J., Campbell R., Williams H., Lawson Y. Antigen-specific T-cell factor in cell cooperation: physical properties and mapping in the left-hand (K) half of H-2. J Exp Med. 1974 Dec 1;140(6):1579–1587. doi: 10.1084/jem.140.6.1579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Schimpl A., Wecker E. Replacement of T-cell function by a T-cell product. Nat New Biol. 1972 May 3;237(70):15–17. doi: 10.1038/newbio237015a0. [DOI] [PubMed] [Google Scholar]
  16. Sonoda S., Schlamowitz M. Studies of 125I trace labeling of immunoglobulin G by chloramine-T. Immunochemistry. 1970 Nov;7(11):885–898. doi: 10.1016/0019-2791(70)90051-0. [DOI] [PubMed] [Google Scholar]
  17. Taussig M. J., Munro A. J., Campbell R., David C. S., Staines N. A. Antigen-specific T-cell factor in cell cooperation. Mapping within the I region of the H-2 complex and ability to cooperate across allogeneic barriers. J Exp Med. 1975 Sep 1;142(3):694–700. doi: 10.1084/jem.142.3.694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Taussig M. J. T cell factor which can replace T cells in vivo. Nature. 1974 Mar 15;248(445):234–236. doi: 10.1038/248234a0. [DOI] [PubMed] [Google Scholar]
  19. Tiollais P., Galibert F., Boiron M. Effects of valine deprivation on the biosynthesis of ribosomal and messenger RNA in a mammalian cell line (L 5178 Y). Eur J Biochem. 1971 Jan 1;18(1):35–45. doi: 10.1111/j.1432-1033.1971.tb01211.x. [DOI] [PubMed] [Google Scholar]
  20. Waldmann H., Munro A. T cell-dependent mediator in the immune response. II. Physical and biological properties. Immunology. 1974 Jul;27(1):53–64. [PMC free article] [PubMed] [Google Scholar]
  21. Waldmann H., Pope H., Munro A. J. Cooperation across the histocompatibility barrier. Nature. 1975 Dec 25;258(5537):728–730. doi: 10.1038/258728a0. [DOI] [PubMed] [Google Scholar]
  22. Waldmann H., Poulton P., Desaymard C. Antigen-non-specific T-cell factor in B-cell activation. Origin, biological properties and failure to show a relationship to H-2. Immunology. 1976 May;30(5):723–733. [PMC free article] [PubMed] [Google Scholar]
  23. Waldmann H. T cell-dependent mediator in the immune response. III. The role of non-specific factor (NSF) in the in vitro immune response. Immunology. 1975 Mar;28(3):497–507. [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES