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. 1994 Jan 1;179(1):135–143. doi: 10.1084/jem.179.1.135

Interleukin 13 is a B cell stimulating factor

PMCID: PMC2191343  PMID: 7903680

Abstract

The recently cloned human interleukin 13 (IL-13) is a novel cytokine expressed in activated T cells that has been shown to inhibit inflammatory cytokine production by lipopolysaccharide-activated monocytes. The protein encoded by the IL-13 cDNA is the human homologue of a mouse Th2-product called P600. Here, we show that IL-13 acts at different stages of the B cell maturation pathway: (a) it enhances the expression of CD23/Fc epsilon RII and class II MHC antigens on resting B cells; (b) it stimulates B cell proliferation in combination with anti-Ig and anti-CD40 antibodies; and (c) it induces IgE synthesis. Thus, the spectrum of the biological activities of IL-13 on B cells largely overlaps that previously ascribed to IL-4. The present observations suggest that IL-13 may be an important factor, in addition to IL-4, in the development of allergic diseases.

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Selected References

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  1. Brown K. D., Zurawski S. M., Mosmann T. R., Zurawski G. A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes. J Immunol. 1989 Jan 15;142(2):679–687. [PubMed] [Google Scholar]
  2. Cher D. J., Mosmann T. R. Two types of murine helper T cell clone. II. Delayed-type hypersensitivity is mediated by TH1 clones. J Immunol. 1987 Jun 1;138(11):3688–3694. [PubMed] [Google Scholar]
  3. Cherwinski H. M., Schumacher J. H., Brown K. D., Mosmann T. R. Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies. J Exp Med. 1987 Nov 1;166(5):1229–1244. doi: 10.1084/jem.166.5.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clark E. A., Ledbetter J. A. Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4494–4498. doi: 10.1073/pnas.83.12.4494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Defrance T., Aubry J. P., Rousset F., Vanbervliet B., Bonnefoy J. Y., Arai N., Takebe Y., Yokota T., Lee F., Arai K. Human recombinant interleukin 4 induces Fc epsilon receptors (CD23) on normal human B lymphocytes. J Exp Med. 1987 Jun 1;165(6):1459–1467. doi: 10.1084/jem.165.6.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Defrance T., Vanbervliet B., Aubry J. P., Banchereau J. Interleukin 4 inhibits the proliferation but not the differentiation of activated human B cells in response to interleukin 2. J Exp Med. 1988 Oct 1;168(4):1321–1337. doi: 10.1084/jem.168.4.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Defrance T., Vanbervliet B., Brière F., Durand I., Rousset F., Banchereau J. Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A. J Exp Med. 1992 Mar 1;175(3):671–682. doi: 10.1084/jem.175.3.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Defrance T., Vanbervliet B., Durand I., Briolay J., Banchereau J. Proliferation and differentiation of human CD5+ and CD5- B cell subsets activated through their antigen receptors or CD40 antigens. Eur J Immunol. 1992 Nov;22(11):2831–2839. doi: 10.1002/eji.1830221112. [DOI] [PubMed] [Google Scholar]
  9. Defrance T., Vanbervliet B., Pène J., Banchereau J. Human recombinant IL-4 induces activated B lymphocytes to produce IgG and IgM. J Immunol. 1988 Sep 15;141(6):2000–2005. [PubMed] [Google Scholar]
  10. Fanslow W. C., Spriggs M. K., Rauch C. T., Clifford K. N., Macduff B. M., Ziegler S. F., Schooley K. A., Mohler K. M., March C. J., Armitage R. J. Identification of a distinct low-affinity receptor for human interleukin-4 on pre-B cells. Blood. 1993 Jun 1;81(11):2998–3005. [PubMed] [Google Scholar]
  11. Gascan H., Gauchat J. F., Roncarolo M. G., Yssel H., Spits H., de Vries J. E. Human B cell clones can be induced to proliferate and to switch to IgE and IgG4 synthesis by interleukin 4 and a signal provided by activated CD4+ T cell clones. J Exp Med. 1991 Mar 1;173(3):747–750. doi: 10.1084/jem.173.3.747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Holder M. J., Liu Y. J., Defrance T., Flores-Romo L., MacLennan I. C., Gordon J. Growth factor requirements for the stimulation of germinal center B cells: evidence for an IL-2-dependent pathway of development. Int Immunol. 1991 Dec;3(12):1243–1251. doi: 10.1093/intimm/3.12.1243. [DOI] [PubMed] [Google Scholar]
  13. Jelinek D. F., Lipsky P. E. Inhibitory influence of IL-4 on human B cell responsiveness. J Immunol. 1988 Jul 1;141(1):164–173. [PubMed] [Google Scholar]
  14. Kim J., Woods A., Becker-Dunn E., Bottomly K. Distinct functional phenotypes of cloned Ia-restricted helper T cells. J Exp Med. 1985 Jul 1;162(1):188–201. doi: 10.1084/jem.162.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kopf M., Le Gros G., Bachmann M., Lamers M. C., Bluethmann H., Köhler G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature. 1993 Mar 18;362(6417):245–248. doi: 10.1038/362245a0. [DOI] [PubMed] [Google Scholar]
  16. Kühn R., Rajewsky K., Müller W. Generation and analysis of interleukin-4 deficient mice. Science. 1991 Nov 1;254(5032):707–710. doi: 10.1126/science.1948049. [DOI] [PubMed] [Google Scholar]
  17. Minty A., Chalon P., Derocq J. M., Dumont X., Guillemot J. C., Kaghad M., Labit C., Leplatois P., Liauzun P., Miloux B. Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature. 1993 Mar 18;362(6417):248–250. doi: 10.1038/362248a0. [DOI] [PubMed] [Google Scholar]
  18. Miyajima A., Kitamura T., Harada N., Yokota T., Arai K. Cytokine receptors and signal transduction. Annu Rev Immunol. 1992;10:295–331. doi: 10.1146/annurev.iy.10.040192.001455. [DOI] [PubMed] [Google Scholar]
  19. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  20. Mosmann T. R., Schumacher J. H., Street N. F., Budd R., O'Garra A., Fong T. A., Bond M. W., Moore K. W., Sher A., Fiorentino D. F. Diversity of cytokine synthesis and function of mouse CD4+ T cells. Immunol Rev. 1991 Oct;123:209–229. doi: 10.1111/j.1600-065x.1991.tb00612.x. [DOI] [PubMed] [Google Scholar]
  21. Rigley K. P., Thurstan S. M., Callard R. E. Independent regulation of interleukin 4 (IL-4)-induced expression of human B cell surface CD23 and IgM: functional evidence for two IL-4 receptors. Int Immunol. 1991 Feb;3(2):197–203. doi: 10.1093/intimm/3.2.197. [DOI] [PubMed] [Google Scholar]
  22. Rousset F., Garcia E., Banchereau J. Cytokine-induced proliferation and immunoglobulin production of human B lymphocytes triggered through their CD40 antigen. J Exp Med. 1991 Mar 1;173(3):705–710. doi: 10.1084/jem.173.3.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rousset F., Garcia E., Defrance T., Péronne C., Vezzio N., Hsu D. H., Kastelein R., Moore K. W., Banchereau J. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1890–1893. doi: 10.1073/pnas.89.5.1890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sautès C., Varin N., Teillaud C., Daëron M., Even J., Hogarth P. M., Fridman W. H. Soluble Fc gamma receptors II (Fc gamma RII) are generated by cleavage of membrane Fc gamma RII. Eur J Immunol. 1991 Jan;21(1):231–234. doi: 10.1002/eji.1830210135. [DOI] [PubMed] [Google Scholar]
  25. Vercelli D., Jabara H. H., Arai K., Geha R. S. Induction of human IgE synthesis requires interleukin 4 and T/B cell interactions involving the T cell receptor/CD3 complex and MHC class II antigens. J Exp Med. 1989 Apr 1;169(4):1295–1307. doi: 10.1084/jem.169.4.1295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zhang X., Polla B., Hauser C., Zubler R. H. T cells from atopic individuals produce IgE-inducing activity incompletely blocked by anti-interleukin-4 antibody. Eur J Immunol. 1992 Mar;22(3):829–833. doi: 10.1002/eji.1830220330. [DOI] [PubMed] [Google Scholar]
  27. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. te Velde A. A., Huijbens R. J., Heije K., de Vries J. E., Figdor C. G. Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes. Blood. 1990 Oct 1;76(7):1392–1397. [PubMed] [Google Scholar]

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