Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Sep 1;168(3):853–862. doi: 10.1084/jem.168.3.853

Interleukin 4 causes isotype switching to IgE in T cell-stimulated clonal B cell cultures

PMCID: PMC2189023  PMID: 3049907

Abstract

Although it has been established that IL-4 enhances both IgG1 and IgE secretion in LPS-stimulated B cell cultures, these studies failed to determine whether IL-4 preferentially induces isotype switching or preferentially allows for the maturation of precommitted precursor cells. To distinguish between these possibilities, it is necessary to ascertain the effect of IL-4 on the isotypes secreted by individual precursor cells during clonal expansion. Therefore, clonal cultures of B cells stimulated with a Th2 helper cell line specific for rabbit Ig and rabbit anti-mouse IgM were established. The majority of B cells are capable of undergoing clonal expansion under these conditions. To vary the level of IL-4 present, either IL-4 or anti-IL-4 was added to cultures. In the presence of IL-4 there was an increase in the proportion of clones that secreted IgE and a decrease in the proportion of clones that secreted IgM. The addition of IL-4 to cultures also increased the amount of IgE secreted by individual clones. Thus, these experiments definitively prove that IL-4 causes specific heavy chain class switching to IgE in Th2-stimulated B cell cultures. In contrast, IL-4 does not affect the proportion of clones secreting IgG1, suggesting that other consequences of Th cell-B cell interactions play a role in the generation of an IgG1 response.

Full Text

The Full Text of this article is available as a PDF (672.8 KB).

Selected References

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

  1. Boom W. H., Liano D., Abbas A. K. Heterogeneity of helper/inducer T lymphocytes. II. Effects of interleukin 4- and interleukin 2-producing T cell clones on resting B lymphocytes. J Exp Med. 1988 Apr 1;167(4):1350–1363. doi: 10.1084/jem.167.4.1350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Clough E. R., Cebra J. J. Interrelationship of primed B cells with the potential for IgE and/or IgA expression. Mol Immunol. 1983 Sep;20(9):903–915. doi: 10.1016/0161-5890(83)90033-0. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Coffman R. L., Seymour B. W., Lebman D. A., Hiraki D. D., Christiansen J. A., Shrader B., Cherwinski H. M., Savelkoul H. F., Finkelman F. D., Bond M. W. The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immunol Rev. 1988 Feb;102:5–28. doi: 10.1111/j.1600-065x.1988.tb00739.x. [DOI] [PubMed] [Google Scholar]
  7. Finkelman F. D., Katona I. M., Urban J. F., Jr, Snapper C. M., Ohara J., Paul W. E. Suppression of in vivo polyclonal IgE responses by monoclonal antibody to the lymphokine B-cell stimulatory factor 1. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9675–9678. doi: 10.1073/pnas.83.24.9675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Lanzavecchia A. One out of five peripheral blood B lymphocytes is activated to high-rate Ig production by human alloreactive T cell clones. Eur J Immunol. 1983 Oct;13(10):820–824. doi: 10.1002/eji.1830131008. [DOI] [PubMed] [Google Scholar]
  10. Lanzavecchia A., Parodi B. In vitro stimulation of IgE production at a single precursor level by human alloreactive T helper clones. Clin Exp Immunol. 1984 Jan;55(1):197–203. [PMC free article] [PubMed] [Google Scholar]
  11. Layton J. E., Vitetta E. S., Uhr J. W., Krammer P. H. Clonal analysis of B cells induced to secrete IgG by T cell-derived lymphokine(s). J Exp Med. 1984 Dec 1;160(6):1850–1863. doi: 10.1084/jem.160.6.1850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Lichtman A. H., Tony H. P., Parker D. C., Abbas A. K. Antigen presentation by hapten-specific B lymphocytes. IV. Comparative ability of B cells to present specific antigen and anti-immunoglobulin antibody. J Immunol. 1987 May 1;138(9):2822–2825. [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
  18. Pike B. L., Alderson M. R., Nossal G. J. T-independent activation of single B cells: an orderly analysis of overlapping stages in the activation pathway. Immunol Rev. 1987 Oct;99:119–152. doi: 10.1111/j.1600-065x.1987.tb01175.x. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Radbruch A., Müller W., Rajewsky K. Class switch recombination is IgG1 specific on active and inactive IgH loci of IgG1-secreting B-cell blasts. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3954–3957. doi: 10.1073/pnas.83.11.3954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Snapper C. M., Finkelman F. D., Paul W. E. Differential regulation of IgG1 and IgE synthesis by interleukin 4. J Exp Med. 1988 Jan 1;167(1):183–196. doi: 10.1084/jem.167.1.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Snapper C. M., Finkelman F. D., Paul W. E. Regulation of IgG1 and IgE production by interleukin 4. Immunol Rev. 1988 Feb;102:51–75. doi: 10.1111/j.1600-065x.1988.tb00741.x. [DOI] [PubMed] [Google Scholar]
  23. Swain S. L., Dutton R. W. Consequences of the direct interaction of helper T cells with B cells presenting antigen. Immunol Rev. 1987 Oct;99:263–280. doi: 10.1111/j.1600-065x.1987.tb01180.x. [DOI] [PubMed] [Google Scholar]
  24. Teale J. M., Liu F. T., Katz D. H. A clonal analysis of the IgE response and its implications with regard to isotope commitment. J Exp Med. 1981 Apr 1;153(4):783–792. doi: 10.1084/jem.153.4.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tony H. P., Parker D. C. Major histocompatibility complex-restricted, polyclonal B cell responses resulting from helper T cell recognition of antiimmunoglobulin presented by small B lymphocytes. J Exp Med. 1985 Jan 1;161(1):223–241. doi: 10.1084/jem.161.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]

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

RESOURCES