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. 1983 Dec 1;158(6):2024–2039. doi: 10.1084/jem.158.6.2024

Interleukin 2 induces antigen-reactive T cell lines to secrete BCGF-I

PMCID: PMC2187160  PMID: 6606015

Abstract

Antigen-activated T lymphocytes produce within 24 h of stimulation a factor that is indistinguishable biochemically and functionally from the B cell co-stimulating growth factor, BCGF-I, originally identified in induced EL4 supernatants: Supernatants from antigen-stimulated T cell lines are not directly mitogenic for resting B cells, but synergize in an H-2-unrestricted manner with anti-Ig activated B cells to produce polyclonal proliferation but not antibody-forming-cell development; biochemical studies reveal the B cell co-stimulating factor present in antigen-stimulated T cell line supernatants is identical by phenyl Sepharose chromatography and isoelectric focusing (IEF) to EL4 supernatant BCGF-I. We thus conclude that normal T cells produce BCGF-I in response to antigenic stimulation. Analysis of the mechanism of BCGF-I production by antigen-stimulated T cells showed that optimum amounts of BCGF-I were obtained as quickly as 24 h post- stimulation, and that the factor producing cells in the T cell line investigated bore the Lyt-1+2- phenotype. As few as 10(4) T cells produced sufficient BCGF-I to support the proliferation of 5 X 10(4) purified anti-Ig activated B cells. Finally, the activation of normal T cell lines to produce BCGF-I required either antigen presented in the context of syngeneic antigen-presenting cells (APC) or interleukin 2 (IL-2).

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Selected References

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  1. Anderson J., Melchers F. T cell-dependent activation of resting B cells: requirement for both nonspecific unrestricted and antigen-specific Ia-restricted soluble factors. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2497–2501. doi: 10.1073/pnas.78.4.2497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson J., Melchers F. T cell-dependent activation of resting B cells: requirement for both nonspecific unrestricted and antigen-specific Ia-restricted soluble factors. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2497–2501. doi: 10.1073/pnas.78.4.2497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Asano Y., Shigeta M., Fathman C. G., Singer A., Hodes R. J. Role of the major histocompatibility complex in T cell activation of B cell subpopulations. A single monoclonal T helper cell population activates different B cell subpopulations by distinct pathways. J Exp Med. 1982 Aug 1;156(2):350–360. doi: 10.1084/jem.156.2.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bradley T. R., Metcalf D. The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci. 1966 Jun;44(3):287–299. doi: 10.1038/icb.1966.28. [DOI] [PubMed] [Google Scholar]
  5. Farrar J. J., Benjamin W. R., Hilfiker M. L., Howard M., Farrar W. L., Fuller-Farrar J. The biochemistry, biology, and role of interleukin 2 in the induction of cytotoxic T cell and antibody-forming B cell responses. Immunol Rev. 1982;63:129–166. doi: 10.1111/j.1600-065x.1982.tb00414.x. [DOI] [PubMed] [Google Scholar]
  6. Farrar J. J., Fuller-Farrar J., Simon P. L., Hilfiker M. L., Stadler B. M., Farrar W. L. Thymoma production of T cell growth factor (Interleukin 2). J Immunol. 1980 Dec;125(6):2555–2558. [PubMed] [Google Scholar]
  7. Farrar J. J., Howard M., Fuller-Farrar J., Paul W. E. Biochemical and physicochemical characterization of mouse B cell growth factor: a lymphokine distinct from interleukin 2. J Immunol. 1983 Oct;131(4):1838–1842. [PubMed] [Google Scholar]
  8. Hamilton J. A., Stanley E. R., Burgess A. W., Shadduck R. K. Stimulation of macrophage plasminogen activator activity by colony-stimulating factors. J Cell Physiol. 1980 Jun;103(3):435–445. doi: 10.1002/jcp.1041030309. [DOI] [PubMed] [Google Scholar]
  9. Handman E., Burgess A. W. Stimulation by granulocyte-macrophage colony-stimulating factor of Leishmania tropica killing by macrophages. J Immunol. 1979 Mar;122(3):1134–1137. [PubMed] [Google Scholar]
  10. Hecht T. T., Longo D. L., Matis L. A. The relationship between immune interferon production and proliferation in antigen-specific, MHC-restricted T cell lines and clones. J Immunol. 1983 Sep;131(3):1049–1055. [PubMed] [Google Scholar]
  11. Howard M., Farrar J., Hilfiker M., Johnson B., Takatsu K., Hamaoka T., Paul W. E. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982 Mar 1;155(3):914–923. doi: 10.1084/jem.155.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Howard M., Kessler S., Chused T., Paul W. E. Long-term culture of normal mouse B lymphocytes. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5788–5792. doi: 10.1073/pnas.78.9.5788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Howard M., Paul W. E. Regulation of B-cell growth and differentiation by soluble factors. Annu Rev Immunol. 1983;1:307–333. doi: 10.1146/annurev.iy.01.040183.001515. [DOI] [PubMed] [Google Scholar]
  14. Isakson P. C., Puré E., Vitetta E. S., Krammer P. H. T cell-derived B cell differentiation factor(s). Effect on the isotype switch of murine B cells. J Exp Med. 1982 Mar 1;155(3):734–748. doi: 10.1084/jem.155.3.734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kimoto M., Fathman C. G. Antigen-reactive T cell clones. I. Transcomplementing hybrid I-A-region gene products function effectively in antigen presentation. J Exp Med. 1980 Oct 1;152(4):759–770. doi: 10.1084/jem.152.4.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kishmoto T., Ishizaka K. Immunologic and physicochemical properties of enhancing soluble factors for IgG and IgE antibody responses. J Immunol. 1975 Apr;114(4):1177–1184. [PubMed] [Google Scholar]
  17. Lanier L. L., Gutman G. A., Lewis D. E., Griswold S. T., Warner N. L. Monoclonal antibodies against rat immunoglobulin kappa chains. Hybridoma. 1982;1(2):125–131. doi: 10.1089/hyb.1.1982.1.125. [DOI] [PubMed] [Google Scholar]
  18. Leanderson T., Lundgren E., Ruuth E., Borg H., Persson H., Coutinho A. B-cell growth factor: distinction from T-cell growth factor and B-cell maturation factor. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7455–7459. doi: 10.1073/pnas.79.23.7455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Leibson H. J., Marrack P., Kappler J. W. B cell helper factors. I. Requirement for both interleukin 2 and another 40,000 mol wt factor. J Exp Med. 1981 Nov 1;154(5):1681–1693. doi: 10.1084/jem.154.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lernhardt W., Corbel C., Wall R., Melchers F. T-cell hybridomas which produce B lymphocyte replication factors only. Nature. 1982 Nov 25;300(5890):355–357. doi: 10.1038/300355a0. [DOI] [PubMed] [Google Scholar]
  21. Malek T. R., Robb R. J., Shevach E. M. Identification and initial characterization of a rat monoclonal antibody reactive with the murine interleukin 2 receptor-ligand complex. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5694–5698. doi: 10.1073/pnas.80.18.5694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Matis L. A., Longo D. L., Hedrick S. M., Hannum C., Margoliash E., Schwartz R. H. Clonal analysis of the major histocompatibility complex restriction and the fine specificity of antigen recognition in the T cell proliferative response to cytochrome C. J Immunol. 1983 Apr;130(4):1527–1535. [PubMed] [Google Scholar]
  23. Melchers F., Andersson J., Lernhardt W., Schreier M. H. H-2-unrestricted polyclonal maturation without replication of small B cells induced by antigen-activated T cell help factors. Eur J Immunol. 1980 Sep;10(9):679–685. doi: 10.1002/eji.1830100905. [DOI] [PubMed] [Google Scholar]
  24. Nakanishi K., Howard M., Muraguchi A., Farrar J., Takatsu K., Hamaoka T., Paul W. E. Soluble factors involved in B cell differentiation: identification of two distinct T cell-replacing factors (TRF). J Immunol. 1983 May;130(5):2219–2224. [PubMed] [Google Scholar]
  25. Okada M., Sakaguchi N., Yoshimura N., Hara H., Shimizu K., Yoshida N., Yoshizaki K., Kishimoto S., Yamamura Y., Kishimoto T. B cell growth factors and B cell differentiation factor from human T hybridomas. Two distinct kinds of B cell growth factor and their synergism in B cell proliferation. J Exp Med. 1983 Feb 1;157(2):583–590. doi: 10.1084/jem.157.2.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Paige C. J., Schreier M. H., Sidman C. L. Mediators from cloned T helper cell lines affect immunoglobulin expression by B cells. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4756–4760. doi: 10.1073/pnas.79.15.4756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Parker D. C. Separable helper factors support B cell proliferation and maturation to Ig secretion. J Immunol. 1982 Aug;129(2):469–474. [PubMed] [Google Scholar]
  29. Puré E., Isakson P. C., Takatsu K., Hamaoka T., Swain S. L., Dutton R. W., Dennert G., Uhr J. W., Vitetta E. S. Induction of B cell differentiation by T cell factors. I. Stimulation of IgM secretion by products of a T cell hybridoma and a T cell line. J Immunol. 1981 Nov;127(5):1953–1958. [PubMed] [Google Scholar]
  30. Robb R. J., Munck A., Smith K. A. T cell growth factor receptors. Quantitation, specificity, and biological relevance. J Exp Med. 1981 Nov 1;154(5):1455–1474. doi: 10.1084/jem.154.5.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schimpl A., Wecker E. A third signal in B cell activation given by TRF. Transplant Rev. 1975;23:176–188. doi: 10.1111/j.1600-065x.1975.tb00157.x. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Swain S. L., Dennert G., Warner J. F., Dutton R. W. Culture supernatants of a stimulated T-cell line have helper activity that acts synergistically with interleukin 2 in the response of B cells to antigen. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2517–2521. doi: 10.1073/pnas.78.4.2517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Swain S. L., Howard M., Kappler J., Marrack P., Watson J., Booth R., Wetzel G. D., Dutton R. W. Evidence for two distinct classes of murine B cell growth factors with activities in different functional assays. J Exp Med. 1983 Sep 1;158(3):822–835. doi: 10.1084/jem.158.3.822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Swain S. L., Wetzel G. D., Soubiran P., Dutton R. W. T cell replacing factors in the B cell response to antigen. Immunol Rev. 1982;63:111–128. doi: 10.1111/j.1600-065x.1982.tb00413.x. [DOI] [PubMed] [Google Scholar]
  36. Takatsu K., Tanaka K., Tominaga A., Kumahara Y., Hamaoka T. Antigen-induced T cell-replacing factor (TRF). III. Establishment of T cell hybrid clone continuously producing TRF and functional analysis of released TRF. J Immunol. 1980 Dec;125(6):2646–2653. [PubMed] [Google Scholar]
  37. Vaux D. L., Pike B. L., Nossal G. J. Antibody production by single, hapten-specific B lymphocytes: an antigen-driven cloning system free of filler or accessory cells. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7702–7706. doi: 10.1073/pnas.78.12.7702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Watson J., Gillis S., Marbrook J., Mochizuki D., Smith K. A. Biochemical and biological characterization of lymphocyte regulatory molecules. I. Purification of a class of murine lymphokines. J Exp Med. 1979 Oct 1;150(4):849–861. doi: 10.1084/jem.150.4.849. [DOI] [PMC free article] [PubMed] [Google Scholar]

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