Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1983 Sep 1;158(3):822–835. doi: 10.1084/jem.158.3.822

Evidence for two distinct classes of murine B cell growth factors with activities in different functional assays

PMCID: PMC2187105  PMID: 6604127

Abstract

Several previously described B cell growth factor (BCGF) activities from a number of mouse monoclonal T cell sources were compared in different functional assays. The results indicate that there are two distinct classes of BCGF defined by functional activity and source. BCGF I, whose prototype is (EL4)BCGF, synergized with anti-Ig in the proliferation of normal splenic B cells but had no activity when dextran sulfate (DXS), rather than anti-Ig, was used to costimulate the same source of B cells. BCGF I also failed to directly stimulate BCL1 tumor B cells. In contrast, BCGF II, whose prototype is (DL)BCGF, showed a reciprocal pattern of activity. BCGF II failed to synergize with anti-Ig-costimulated normal B cells to give good proliferative responses. Sources of BCGF II also directly stimulated (no anti-Ig or DXS added) B cells of the BCL1 tumor-carrying mice. These results suggest that the two BCGF may have activity on two subsets of B cells that respond differentially to induction with the two polyclonal B cell activators, anti-Ig and DXS. The possibilities that these different patterns of response occur in separate lineages of B cells and/or in B cells in different states of differentiation is discussed.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

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

  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. Asano Y., Singer A., Hodes R. J. Role of the major histocompatibility complex in T cell activation of B cell subpopulations. Major histocompatibility complex-restricted and -unrestricted B cell responses are mediated by distinct B cell subpopulations. J Exp Med. 1981 Oct 1;154(4):1100–1115. doi: 10.1084/jem.154.4.1100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Defranco A. L., Raveche E. S., Asofsky R., Paul W. E. Frequency of B lymphocytes responsive to anti-immunoglobulin. J Exp Med. 1982 May 1;155(5):1523–1536. doi: 10.1084/jem.155.5.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gronowicz E., Coutinho A. Selective triggering of B cell subpopulations by mitogens. Eur J Immunol. 1974 Nov;4(11):771–776. doi: 10.1002/eji.1830041113. [DOI] [PubMed] [Google Scholar]
  5. Harwell L., Skidmore B., Marrack P., Kappler J. Concanavalin A-inducible, interleukin-2-producing T cell hybridoma. J Exp Med. 1980 Oct 1;152(4):893–904. doi: 10.1084/jem.152.4.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Howard M., Mizel S. B., Lachman L., Ansel J., Johnson B., Paul W. E. Role of interleukin 1 in anti-immunoglobulin-induced B cell proliferation. J Exp Med. 1983 May 1;157(5):1529–1543. doi: 10.1084/jem.157.5.1529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Isakson P. C., Puré E., Uhr J. W., Vitetta E. S. Induction of proliferation and differentiation of neoplastic B cells by anti-immunoglobulin and T-cell factors. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2507–2511. doi: 10.1073/pnas.78.4.2507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kincade P. W. Defective colony formation by B lymphocytes from CBA/N and C3H/HeJ mice. J Exp Med. 1977 Feb 1;145(2):249–263. doi: 10.1084/jem.145.2.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Knapp M. R., Severinson-Gronowicz E., Schröder J., Strober S. Characterization of a spontaneous murine B cell leukemia (BCL1). II. Tumor cell proliferation and IgM secretion after stimulation by LPS. J Immunol. 1979 Sep;123(3):1000–1006. [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. 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]
  15. Maizel A., Sahasrabuddhe C., Mehta S., Morgan J., Lachman L., Ford R. Biochemical separation of a human B cell mitogenic factor. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5998–6002. doi: 10.1073/pnas.79.19.5998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Muraguchi A., Butler J. L., Kehrl J. H., Fauci A. S. Differential sensitivity of human B cell subsets to activation signals delivered by anti-mu antibody and proliferative signals delivered by a monoclonal B cell growth factor. J Exp Med. 1983 Feb 1;157(2):530–546. doi: 10.1084/jem.157.2.530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Parker D. C. Induction and suppression of polyclonal antibody responses by anti-Ig reagents and antigen-nonspecific helper factors: a comparison of the effects of anti-Fab, anti-IgM, and anti IgD on murine B cells. Immunol Rev. 1980;52:115–139. doi: 10.1111/j.1600-065x.1980.tb00333.x. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Pike B. L., Vaux D. L., Clark-Lewis I., Schrader J. W., Nossal G. J. Proliferation and differentiation of single hapten-specific B lymphocytes is promoted by T-cell factor(s) distinct from T-cell growth factor. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6350–6354. doi: 10.1073/pnas.79.20.6350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pure E., Isakson P. C., Kappler J. W., Marrack P., Krammer P. H., Vitetta E. S. T cell-derived B cell growth and differentiation factors. Dichotomy between the responsiveness of B cells from adult and neonatal mice. J Exp Med. 1983 Feb 1;157(2):600–612. doi: 10.1084/jem.157.2.600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Scher I. CBA/N immune defective mice; evidence for the failure of a B cell subpopulation to be expressed. Immunol Rev. 1982;64:117–136. doi: 10.1111/j.1600-065x.1982.tb00421.x. [DOI] [PubMed] [Google Scholar]
  25. Singer A., Asano Y., Shigeta M., Hathcock K. S., Ahmed A., Fathman C. G., Hodes R. J. Distinct B cell subpopulations differ in their genetic requirements for activation by T helper cells. Immunol Rev. 1982;64:137–160. doi: 10.1111/j.1600-065x.1982.tb00422.x. [DOI] [PubMed] [Google Scholar]
  26. Slavin S., Strober S. Spontaneous murine B-cell leukaemia. Nature. 1978 Apr 13;272(5654):624–626. doi: 10.1038/272624a0. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Swain S. L., Dutton R. W. Production of a B cell growth-promoting activity, (DL)BCGF, from a cloned T cell line and its assay on the BCL1 B cell tumor. J Exp Med. 1982 Dec 1;156(6):1821–1834. doi: 10.1084/jem.156.6.1821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Thoman M. L., Weigle W. O. Identification and partial purification of a B cell growth-promoting material utilizing the BCL1 cell line. J Immunol. 1983 Jan;130(1):233–236. [PubMed] [Google Scholar]
  31. 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]
  32. Wetzel G. D., Kettman J. R. Activation of murine B cells. II. Dextran sulfate removes the requirement for cellular interaction during lipopolysaccharide-induced mitogenesis. Cell Immunol. 1981 Jun;61(1):176–189. doi: 10.1016/0008-8749(81)90364-6. [DOI] [PubMed] [Google Scholar]
  33. Wetzel G. D., Kettman J. R. Activation of murine B lymphocytes. III. Stimulation of B lymphocyte clonal growth with lipopolysaccharide and dextran sulfate. J Immunol. 1981 Feb;126(2):723–728. [PubMed] [Google Scholar]
  34. Wetzel G. D., Swain S. L., Dutton R. W. A monoclonal T cell-replacing activity can act directly on B cells to enhance clonal expansion. J Exp Med. 1982 Jul 1;156(1):306–311. doi: 10.1084/jem.156.1.306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Whitlock C. A., Watson J. D. B-cell differentiation in the CBA/N mouse. I. Slower maturation of mitogen and antigen-responsive B cells in mice expressing an X-linked defect. J Exp Med. 1979 Dec 1;150(6):1483–1497. doi: 10.1084/jem.150.6.1483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Yoshizaki K., Nakagawa T., Fukunaga K., Kaieda T., Maruyama S., Kishimoto S., Yamamura Y., Kishimoto T. Characterization of human B cell growth factor (BCGF) from cloned T cells or mitogen-stimulated T cells. J Immunol. 1983 Mar;130(3):1241–1246. [PubMed] [Google Scholar]
  37. Yoshizaki K., Nakagawa T., Kaieda T., Muraguchi A., Yamamura Y., Kishimoto T. Induction of proliferation and Ig production in human B leukemic cells by anti-immunoglobulins and T cell factors. J Immunol. 1982 Mar;128(3):1296–1301. [PubMed] [Google Scholar]

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

RESOURCES