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. 1987 Mar;84(5):1389–1393. doi: 10.1073/pnas.84.5.1389

Single cell studies on the role of B-cell stimulatory factor 1 in B-cell activation.

M R Alderson, B L Pike, G J Nossal
PMCID: PMC304435  PMID: 3493492

Abstract

The role of the T-cell-derived lymphokine B-cell stimulatory factor 1 (BSF-1) in the early activation, proliferation, and antibody-forming cell (AFC) clone formation of single fluorescein-specific B lymphocytes isolated from normal mouse spleens by hapten-gelatin adherence has been studied in vitro. BSF-1 acting alone induced early B-cell activation, as assessed by a significant increase in cell diameter of single B cells cultured for 24 hr. A small but significant number of these B cells formed proliferating clones, some of which secreted antibody. When acting with the specific antigen fluorescein-polymerized flagellin, BSF-1 augmented early cell enlargement and markedly enhanced proliferation, but it did not increase the frequency of AFC clones stimulated by fluorescein-polymerized flagellin alone. The further addition of recombinant murine interleukin 1 (IL-1) marginally enhanced proliferation caused by antigen plus BSF-1. No synergy was observed between BSF-1 and IL-1 for antibody formation. In the presence of fibroblast filler cells, BSF-1 substantially inhibited AFC clone development achieved by antigen plus IL-1. BSF-1 was also found to be inhibitory to AFC clone development stimulated by specific antigen acting with either recombinant human interleukin 2 (IL-2) or with IL-2 plus IL-1, both in the presence or absence of filler cells. The results suggest that BSF-1 plays a complex role in the regulation of the B-cell activation pathway by enhancing early activation and antigen-specific proliferation as well as inhibiting the effects of other B-cell factors on antibody formation. BSF-1 is the only cytokine so far tested in the single B-cell system that acts with antigen to promote proliferation without concomitant antibody production.

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Selected References

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  1. Coffman R. L., Carty J. A T cell activity that enhances polyclonal IgE production and its inhibition by interferon-gamma. J Immunol. 1986 Feb 1;136(3):949–954. [PubMed] [Google Scholar]
  2. Coffman R. L., Ohara J., Bond M. W., Carty J., Zlotnik A., Paul W. E. B cell stimulatory factor-1 enhances the IgE response of lipopolysaccharide-activated B cells. J Immunol. 1986 Jun 15;136(12):4538–4541. [PubMed] [Google Scholar]
  3. Grabstein K., Eisenman J., Mochizuki D., Shanebeck K., Conlon P., Hopp T., March C., Gillis S. Purification to homogeneity of B cell stimulating factor. A molecule that stimulates proliferation of multiple lymphokine-dependent cell lines. J Exp Med. 1986 Jun 1;163(6):1405–1414. doi: 10.1084/jem.163.6.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Lee F., Yokota T., Otsuka T., Meyerson P., Villaret D., Coffman R., Mosmann T., Rennick D., Roehm N., Smith C. Isolation and characterization of a mouse interleukin cDNA clone that expresses B-cell stimulatory factor 1 activities and T-cell- and mast-cell-stimulating activities. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2061–2065. doi: 10.1073/pnas.83.7.2061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lomedico P. T., Gubler U., Hellmann C. P., Dukovich M., Giri J. G., Pan Y. C., Collier K., Semionow R., Chua A. O., Mizel S. B. Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. 1984 Nov 29-Dec 5Nature. 312(5993):458–462. doi: 10.1038/312458a0. [DOI] [PubMed] [Google Scholar]
  8. Mizel S. B., Dukovich M., Rothstein J. Preparation of goat antibodies against interleukin 1: use of an immunoadsorbent to purify interleukin 1. J Immunol. 1983 Oct;131(4):1834–1837. [PubMed] [Google Scholar]
  9. Mosmann T. R., Bond M. W., Coffman R. L., Ohara J., Paul W. E. T-cell and mast cell lines respond to B-cell stimulatory factor 1. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5654–5658. doi: 10.1073/pnas.83.15.5654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Nakanishi K., Malek T. R., Smith K. A., Hamaoka T., Shevach E. M., Paul W. E. Both interleukin 2 and a second T cell-derived factor in EL-4 supernatant have activity as differentiation factors in IgM synthesis. J Exp Med. 1984 Dec 1;160(6):1605–1621. doi: 10.1084/jem.160.6.1605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Noelle R., Krammer P. H., Ohara J., Uhr J. W., Vitetta E. S. Increased expression of Ia antigens on resting B cells: an additional role for B-cell growth factor. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6149–6153. doi: 10.1073/pnas.81.19.6149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Noma Y., Sideras P., Naito T., Bergstedt-Lindquist S., Azuma C., Severinson E., Tanabe T., Kinashi T., Matsuda F., Yaoita Y. Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter. Nature. 1986 Feb 20;319(6055):640–646. doi: 10.1038/319640a0. [DOI] [PubMed] [Google Scholar]
  13. Nossal G. J., Pike B. L., Battye F. L. Sequential use of hapten-gelatin fractionation and fluorescence-activated cell sorting in the enrichment of hapten-specific B llymphocytes. Eur J Immunol. 1978 Mar;8(3):151–157. doi: 10.1002/eji.1830080302. [DOI] [PubMed] [Google Scholar]
  14. Nossal G. J., Pike B. L. Single cell studies on the antibody-forming potential of fractionated, hapten-specific B lymphocytes. Immunology. 1976 Feb;30(2):189–202. [PMC free article] [PubMed] [Google Scholar]
  15. Ohara J., Paul W. E. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. doi: 10.1038/315333a0. [DOI] [PubMed] [Google Scholar]
  16. Oliver K., Noelle R. J., Uhr J. W., Krammer P. H., Vitetta E. S. B-cell growth factor (B-cell growth factor I or B-cell-stimulating factor, provisional 1) is a differentiation factor for resting B cells and may not induce cell growth. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2465–2467. doi: 10.1073/pnas.82.8.2465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pike B. L., Nossal G. J. A high-efficiency cloning system for single hapten-specific B lymphocytes that is suitable for assay of putative growth and differentiation factors. Proc Natl Acad Sci U S A. 1985 May;82(10):3395–3399. doi: 10.1073/pnas.82.10.3395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pike B. L., Nossal G. J. A reappraisal of "T-independent" antigens. I. Effect of lymphokines on the response of single adult hapten-specific B lymphocytes. J Immunol. 1984 Apr;132(4):1687–1695. [PubMed] [Google Scholar]
  19. Pike B. L., Nossal G. J. Interleukin 1 can act as a B-cell growth and differentiation factor. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8153–8157. doi: 10.1073/pnas.82.23.8153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pike B. L., Raubitschek A., Nossal G. J. Human interleukin 2 can promote the growth and differentiation of single hapten-specific B cells in the presence of specific antigen. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7917–7921. doi: 10.1073/pnas.81.24.7917. [DOI] [PMC free article] [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. Pike B. L., Vaux D. L., Nossal G. J. Single cell studies on hapten-specific B lymphocytes: differential cloning efficiency of cells of various sizes. J Immunol. 1983 Aug;131(2):554–560. [PubMed] [Google Scholar]
  23. Polla B. S., Poljak A., Geier S. G., Nathenson S. G., Ohara J., Paul W. E., Glimcher L. H. Three distinct signals can induce class II gene expression in a murine pre-B-cell line. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4878–4882. doi: 10.1073/pnas.83.13.4878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rabin E. M., Ohara J., Paul W. E. B-cell stimulatory factor 1 activates resting B cells. Proc Natl Acad Sci U S A. 1985 May;82(9):2935–2939. doi: 10.1073/pnas.82.9.2935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rosenberg S. A., Grimm E. A., McGrogan M., Doyle M., Kawasaki E., Koths K., Mark D. F. Biological activity of recombinant human interleukin-2 produced in Escherichia coli. Science. 1984 Mar 30;223(4643):1412–1414. doi: 10.1126/science.6367046. [DOI] [PubMed] [Google Scholar]
  26. Stein P., Dubois P., Greenblatt D., Howard M. Induction of antigen-specific proliferation in affinity-purified small B lymphocytes: requirement for BSF-1 by type 2 but not type 1 thymus-independent antigens. J Immunol. 1986 Mar 15;136(6):2080–2089. [PubMed] [Google Scholar]
  27. Suter M., Pike B. L., Nossal G. J. An ELISA assay efficiently detects clonal antibody formation by single, hapten-specific B lymphocytes. J Immunol Methods. 1985 Nov 28;84(1-2):327–341. doi: 10.1016/0022-1759(85)90440-5. [DOI] [PubMed] [Google Scholar]
  28. Thompson C. B., Schaefer M. E., Finkelman F. D., Scher I., Farrar J., Mond J. J. T cell-derived B cell growth factor(s) can induce stimulation of both resting and activated B cells. J Immunol. 1985 Jan;134(1):369–374. [PubMed] [Google Scholar]
  29. 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]
  30. Vitetta E. S., Ohara J., Myers C. D., Layton J. E., Krammer P. H., Paul W. E. Serological, biochemical, and functional identity of B cell-stimulatory factor 1 and B cell differentiation factor for IgG1. J Exp Med. 1985 Nov 1;162(5):1726–1731. doi: 10.1084/jem.162.5.1726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Zubler R. H., Lowenthal J. W., Erard F., Hashimoto N., Devos R., MacDonald H. R. Activated B cells express receptors for, and proliferate in response to, pure interleukin 2. J Exp Med. 1984 Oct 1;160(4):1170–1183. doi: 10.1084/jem.160.4.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]

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