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. 1983 Feb 1;157(2):600–612. doi: 10.1084/jem.157.2.600

T cell-derived B cell growth and differentiation factors. Dichotomy between the responsiveness of B cells from adult and neonatal mice

PMCID: PMC2186917  PMID: 6600488

Abstract

In these studies we have determined the molecular weights of B cell growth factor (BCGF) (less than 20,000), and B cell differentiation factors (BCDF) that induce immunoglobulin M (IgM) secretion (BCDF mu) (30-60,000) and IgG secretion (BCDF gamma) (less than 20,000). Thus, the molecular weight of BCDF mu is distinct from that of BCGF and BCDF gamma; BCGF and BCDF gamma cannot be distinguished. In addition, BCGF, BCDF mu, and BCDF gamma are distinguishable by their presence or absence in different supernatants from a panel of mitogen-induced T cell clones. These results suggest that the three lymphokines are different. This conclusion is supported by their differential biological effect on B cells from adult and neonatal mice. Thus, treatment with anti-Ig induces B cells from adult mice to proliferate and this proliferation is sustained by BCGF. In contrast, even in the presence of BCGF, anti-Ig does not induce B cells from neonatal mice to proliferate. However, BCDF mu and BCDF gamma induce IgM and IgG secretion in B cells, respectively, from both adult and neonatal mice. Thus, mature B cells can both clonally expand and differentiate in response to anti-Ig, BCGF, and BCDF, whereas immature B cells can only differentiate. The poor response of neonatal B cells to anti-Ig and BCGF may partially explain the relative immunoincompetence of immature B cells.

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Selected References

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  1. Andersson J., Schreier M. H., Melchers F. T-cell-dependent B-cell stimulation is H-2 restricted and antigen dependent only at the resting B-cell level. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1612–1616. doi: 10.1073/pnas.77.3.1612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Armerding D., Sachs D. H., Katz D. H. Activation of T and B lymphocytes in vitro. III. Presence of Ia determinants on allogeneic effect factor. J Exp Med. 1974 Dec 1;140(6):1717–1722. doi: 10.1084/jem.140.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cambier J. C., Kettman J. R., Vitetta E. S., Uhr J. W. Differential susceptibility of neonatal and adult murine spleen cells to in vitro induction of B-cell tolerance. J Exp Med. 1976 Jul 1;144(1):293–297. doi: 10.1084/jem.144.1.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Corvese J. S., Levy E. M., Bennett M., Cooperband S. R. Inhibition of an in vitro antibody response by a suppressor cell in normal bone marrow. Cell Immunol. 1980 Feb;49(2):293–306. doi: 10.1016/0008-8749(80)90031-3. [DOI] [PubMed] [Google Scholar]
  5. Delovitch T. L., Biggin J., Fung F. Y. In vitro analysis of allogeneic lymphocyte interaction. II. I-region control of the activity of a B-cell-derived H-2-restricted allogeneic effect factor and its receptor during B-cell activation. J Exp Med. 1978 Apr 1;147(4):1198–1212. doi: 10.1084/jem.147.4.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Delovitch T. L., Watson J., Battistella R., Harris J. F., Shaw J., Paetkau V. In vitro analysis of allogeneic lymphocyte interaction. V. Identification and characterization of two components of allogeneic effect factor, one of which displays H-2-restricted helper activity and the other, T cell-growth factor activity. J Exp Med. 1981 Jan 1;153(1):107–128. doi: 10.1084/jem.153.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Duwe A. K., Singhal S. K. The immunoregulatory role of bone marrow. I. Suppression of the induction of antibody responses to T-dependent and T-independent antigens by cells in the bone marrow. Cell Immunol. 1979 Mar 15;43(2):362–371. doi: 10.1016/0008-8749(79)90180-1. [DOI] [PubMed] [Google Scholar]
  9. Elson C. O., Heck J. A., Strober W. T-cell regulation of murine IgA synthesis. J Exp Med. 1979 Mar 1;149(3):632–643. doi: 10.1084/jem.149.3.632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Ford R. J., Mehta S. R., Franzini D., Montagna R., Lachman L. B., Maizel A. L. Soluble factor activation of human B lymphocytes. Nature. 1981 Nov 19;294(5838):261–263. doi: 10.1038/294261a0. [DOI] [PubMed] [Google Scholar]
  12. Glasebrook A. L., Quintans J., Eisenberg L., Fitch F. W. Alloreactive cloned T cell lines. II. Polyclonal stimulation of B cells by a cloned helper T cell line. J Immunol. 1981 Jan;126(1):240–244. [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Isakson P. C., Krolick K. A., Uhr J. W., Vitetta E. S. The effect of anti-immunoglobulin antibodies on the in vitro proliferation and differentiation of normal and neoplastic murineB cells. J Immunol. 1980 Aug;125(2):886–892. [PubMed] [Google Scholar]
  16. 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]
  17. Julius M. H., von Boehmer H., Sidman C. L. Dissociation of two signals required for activation of resting B cells. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1989–1993. doi: 10.1073/pnas.79.6.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kearney J. F., Lawton A. R. B lymphocyte differentiation induced by lipopolysaccharide. II. Response of fetal lymphocytes. J Immunol. 1975 Sep;115(3):677–681. [PubMed] [Google Scholar]
  20. 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]
  21. Krolick K. A., Isakson P. C., Uhr J. W., Vitetta E. S. Murine B cell leukemia (BCL1): organ distribution and kinetics of growth as determined by fluorescence analysis with an anti-idiotypic antibody. J Immunol. 1979 Nov;123(5):1928–1935. [PubMed] [Google Scholar]
  22. Krolick K. A., Villemez C., Isakson P., Uhr J. W., Vitetta E. S. Selective killing of normal or neoplastic B cells by antibodies coupled to the A chain of ricin. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5419–5423. doi: 10.1073/pnas.77.9.5419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. Levy E. M., Corvese J. S., Bennett M. A comparison of the suppressor cells found in the spleens of 89SR-treated mice and in normal murine bone marrow. J Immunol. 1981 Mar;126(3):1090–1094. [PubMed] [Google Scholar]
  27. Martinez-Alonso C., Coutinho A., Augustin A. A. Immunoglobulin C-gene expression. I. The commitment to IgG subclass of secretory cells is determined by the quality of the nonspecific stimuli. Eur J Immunol. 1980 Sep;10(9):698–702. doi: 10.1002/eji.1830100908. [DOI] [PubMed] [Google Scholar]
  28. Mayer L., Fu S. M., Kunkel H. G. Human T cell hybridomas secreting factors for IgA-specific help, polyclonal B cell activation, and B cell proliferation. J Exp Med. 1982 Dec 1;156(6):1860–1865. doi: 10.1084/jem.156.6.1860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Metcalf E. S., Klinman N. R. In vitro tolerance induction of neonatal murine B cells. J Exp Med. 1976 Jun 1;143(6):1327–1340. doi: 10.1084/jem.143.6.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Nabel G., Greenberger J. S., Sakakeeny M. A., Cantor H. Multiple biologic activities of a cloned inducer T-cell population. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1157–1161. doi: 10.1073/pnas.78.2.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. 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]
  33. 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]
  34. Puré E., Vitetta E. S. The murine B cell response to TNP-polyacrylamide beads: the relationship between the epitope density of the antigen and the requirements for T cell help and surface IgD. J Immunol. 1980 Jul;125(1):420–427. [PubMed] [Google Scholar]
  35. Puré E., Vitetta E. Induction of murine B cell proliferation by insolubilized anti-immunoglobulins. J Immunol. 1980 Sep;125(3):1240–1242. [PubMed] [Google Scholar]
  36. 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]
  37. Rosenberg Y. J., Chiller J. M. Ability of antigen-specific helper cells to effect a class-restricted increase in total Ig-secreting cells in spleens after immunization with the antigen. J Exp Med. 1979 Sep 19;150(3):517–530. doi: 10.1084/jem.150.3.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. STERZL J., TRNKA Z. Effect of very large doses of bacterial antigen on antibody production in newborn rabbits. Nature. 1957 May 4;179(4566):918–919. doi: 10.1038/179918a0. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. 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]
  41. Sidman C. L., Unanue E. R. Development of B lymphocytes. I. Cell populations and a critical event during ontogeny. J Immunol. 1975 Jun;114(6):1730–1735. [PubMed] [Google Scholar]
  42. 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]
  43. Sredni B., Sieckmann D. G., Kumagai S., House S., Green I., Paul W. E. Long-term culture and cloning of nontransformed human B lymphocytes. J Exp Med. 1981 Nov 1;154(5):1500–1516. doi: 10.1084/jem.154.5.1500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. 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]
  45. 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]
  46. 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]
  47. Zitron I. M., Clevinger B. L. Regulation of murine B cells through surface immunoglobulin. I. Monoclonal anti-delta antibody that induces allotype-specific proliferation. J Exp Med. 1980 Nov 1;152(5):1135–1146. doi: 10.1084/jem.152.5.1135. [DOI] [PMC free article] [PubMed] [Google Scholar]

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