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. 1994 Aug 1;180(2):727–732. doi: 10.1084/jem.180.2.727

Growth hormone and insulin-like growth factor I induce immunoglobulin (Ig)E and IgG4 production by human B cells

PMCID: PMC2191604  PMID: 8046348

Abstract

We studied the effects of growth hormone (GH), insulin-like growth factor I (IGF-I), IGF-II, and insulin on human immunoglobulin E (IgE) and IgG4 production. GH and IGF-I induced IgE and IgG4 production by normal donors' mononuclear cells (MNC) depleted of sIgE+ and sIgG4+ B cells without affecting IgM, IgG1, IgG2, IgG3, IgA1, or IgA2 production, whereas IGF-II and insulin failed to do so. GH-induced IgE and IgG4 production was specific, and was not mediated by IGF-I, interleukin 4 (IL-4), or IL-13, since it was blocked by anti-GH antibody (Ab), but not by anti-IGF-I Ab, anti-IL-4 Ab, or anti-IL-13 Ab. Conversely, IGF-I-induced IgE and IgG4 production was blocked by anti-IGF-I Ab, but not by anti-GH Ab, anti-IL-4 Ab, or anti-IL-13 Ab. Moreover, interferon alpha (IFN-alpha) or IFN-gamma, which counteracted IL-4-and IL-13-induced IgE and IgG4 production, had no effect on induction by GH or IGF-I. In contrast to MNC, GH or IGF-I failed to induce IgE and IgG4 production by purified sIgE-, sIgG4- B cells. However, in the presence of anti-CD40 monoclonal antibody (mAb), GH or IGF-I induced IgE and IgG4 production by these cells. Purified sIgE+, but not sIgE-, B cells from atopic patients spontaneously produced IgE. GH or IGF-I with anti-CD40 mAb failed to enhance IgE production by sIgE+ B cells, whereas they induced IgE production by sIgE- B cells. Similarly, whereas GH or IGF-I with anti-CD40 mAb failed to enhance IgG4 production by sIgG4+ B cells from atopic patients, they induced IgG4 production by sIgG4- B cells. Again, neither IgE nor IgG4 induction was blocked by anti-IL-4 Ab or anti-IL-13 Ab. These results indicate that GH and IGF-I induce IgE and IgG4 production by class switching in an IL-4- and IL-13-independent mechanism.

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Selected References

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  1. Aversa G., Punnonen J., Cocks B. G., de Waal Malefyt R., Vega F., Jr, Zurawski S. M., Zurawski G., de Vries J. E. An interleukin 4 (IL-4) mutant protein inhibits both IL-4 or IL-13-induced human immunoglobulin G4 (IgG4) and IgE synthesis and B cell proliferation: support for a common component shared by IL-4 and IL-13 receptors. J Exp Med. 1993 Dec 1;178(6):2213–2218. doi: 10.1084/jem.178.6.2213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Fleisher T. A., White R. M., Broder S., Nissley S. P., Blaese R. M., Mulvihill J. J., Olive G., Waldmann T. A. X-linked hypogammaglobulinemia and isolated growth hormone deficiency. N Engl J Med. 1980 Jun 26;302(26):1429–1434. doi: 10.1056/NEJM198006263022601. [DOI] [PubMed] [Google Scholar]
  3. Fu Y. K., Arkins S., Wang B. S., Kelley K. W. A novel role of growth hormone and insulin-like growth factor-I. Priming neutrophils for superoxide anion secretion. J Immunol. 1991 Mar 1;146(5):1602–1608. [PubMed] [Google Scholar]
  4. Geffner M. E., Bersch N., Lippe B. M., Rosenfeld R. G., Hintz R. L., Golde D. W. Growth hormone mediates the growth of T-lymphoblast cell lines via locally generated insulin-like growth factor-I. J Clin Endocrinol Metab. 1990 Aug;71(2):464–469. doi: 10.1210/jcem-71-2-464. [DOI] [PubMed] [Google Scholar]
  5. Gjerset R. A., Yeargin J., Volkman S. K., Vila V., Arya J., Haas M. Insulin-like growth factor-I supports proliferation of autocrine thymic lymphoma cells with a pre-T cell phenotype. J Immunol. 1990 Nov 15;145(10):3497–3501. [PubMed] [Google Scholar]
  6. Hattori N., Shimatsu A., Sugita M., Kumagai S., Imura H. Immunoreactive growth hormone (GH) secretion by human lymphocytes: augmented release by exogenous GH. Biochem Biophys Res Commun. 1990 Apr 30;168(2):396–401. doi: 10.1016/0006-291x(90)92334-v. [DOI] [PubMed] [Google Scholar]
  7. Jabara H. H., Fu S. M., Geha R. S., Vercelli D. CD40 and IgE: synergism between anti-CD40 monoclonal antibody and interleukin 4 in the induction of IgE synthesis by highly purified human B cells. J Exp Med. 1990 Dec 1;172(6):1861–1864. doi: 10.1084/jem.172.6.1861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kimata H., Mikawa H. Nedocromil sodium selectively inhibits IgE and IgG4 production in human B cells stimulated with IL-4. J Immunol. 1993 Dec 15;151(12):6723–6732. [PubMed] [Google Scholar]
  9. Kimata H., Sherr E. H., Saxon A. Human natural killer (NK) cells produce a late-acting B-cell differentiation activity. J Clin Immunol. 1988 Sep;8(5):381–389. doi: 10.1007/BF00917154. [DOI] [PubMed] [Google Scholar]
  10. Kimata H., Yoshida A., Fujimoto M., Mikawa H. Effect of vasoactive intestinal peptide, somatostatin, and substance P on spontaneous IgE and IgG4 production in atopic patients. J Immunol. 1993 May 15;150(10):4630–4640. [PubMed] [Google Scholar]
  11. Kimata H., Yoshida A., Ishioka C., Lindley I., Mikawa H. Interleukin 8 (IL-8) selectively inhibits immunoglobulin E production induced by IL-4 in human B cells. J Exp Med. 1992 Oct 1;176(4):1227–1231. doi: 10.1084/jem.176.4.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kimata H., Yoshida A., Ishioka C., Mikawa H. Differential effect of vasoactive intestinal peptide, somatostatin, and substance P on human IgE and IgG subclass production. Cell Immunol. 1992 Oct 15;144(2):429–442. doi: 10.1016/0008-8749(92)90257-p. [DOI] [PubMed] [Google Scholar]
  13. Kimata H., Yoshida A., Ishioka C., Mikawa H. Effect of recombinant human erythropoietin on human IgE production in vitro. Clin Exp Immunol. 1991 Mar;83(3):483–487. doi: 10.1111/j.1365-2249.1991.tb05665.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Merchav S., Tatarsky I., Hochberg Z. Enhancement of erythropoiesis in vitro by human growth hormone is mediated by insulin-like growth factor I. Br J Haematol. 1988 Nov;70(3):267–271. doi: 10.1111/j.1365-2141.1988.tb02480.x. [DOI] [PubMed] [Google Scholar]
  15. Merimee T. J., Grant M. B., Broder C. M., Cavalli-Sforza L. L. Insulin-like growth factor secretion by human B-lymphocytes: a comparison of cells from normal and pygmy subjects. J Clin Endocrinol Metab. 1989 Nov;69(5):978–984. doi: 10.1210/jcem-69-5-978. [DOI] [PubMed] [Google Scholar]
  16. Punnonen J., Aversa G., Cocks B. G., McKenzie A. N., Menon S., Zurawski G., de Waal Malefyt R., de Vries J. E. Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3730–3734. doi: 10.1073/pnas.90.8.3730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pène J., Rousset F., Brière F., Chrétien I., Bonnefoy J. Y., Spits H., Yokota T., Arai N., Arai K., Banchereau J. IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6880–6884. doi: 10.1073/pnas.85.18.6880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rom W. N., Basset P., Fells G. A., Nukiwa T., Trapnell B. C., Crysal R. G. Alveolar macrophages release an insulin-like growth factor I-type molecule. J Clin Invest. 1988 Nov;82(5):1685–1693. doi: 10.1172/JCI113781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Yoshida A., Ishioka C., Kimata H., Mikawa H. Recombinant human growth hormone stimulates B cell immunoglobulin synthesis and proliferation in serum-free medium. Acta Endocrinol (Copenh) 1992 Jun;126(6):524–529. doi: 10.1530/acta.0.1260524. [DOI] [PubMed] [Google Scholar]
  20. Zhang K., Clark E. A., Saxon A. CD40 stimulation provides an IFN-gamma-independent and IL-4-dependent differentiation signal directly to human B cells for IgE production. J Immunol. 1991 Mar 15;146(6):1836–1842. [PubMed] [Google Scholar]
  21. 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]

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