Regulation of B-cell immune responses: predominant role of interleukin-4 in triggering cell proliferation and Ig production in competent B cells.
We established a system for induction of competence in B cells following brief (45 min) exposure to either the combination of phorbol 12,13-dibutyrate (PDB) and ionomycin (I) (PDB/I) or PDB/anti-IgM. B cells, rendered competent in this fashion, were able to respond to PDB in the second or progression phase of culture but did not proliferate on their own. In addition, competent B cells were IL-2- or IL-4-responsive, due to up-regulation of their respective receptors following competence induction. IL-4 was found to have the most effective role in the progression phase to promote DNA synthesis and was able to enhance both IL-2 and IL-4 receptor expression. Whereas provision of IL-4 could induce IgM, IgG, and IgA in the absence of T cells, it did not result in IgE production. IgE production was only achieved in the presence of activated T cells (competent) together with competent B cells. These results indicate that IL-4 has a major role in B-cell immune responses following initial activation and trigger the cells, in the absence of T cells or other factors, to proliferate and differentiate into Ig-secreting cells. For IgE production in competent B cells, however, IL-4 alone could not overcome the requirement for activated T cells.
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Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
Renz
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Terada
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Gelfand
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D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000917:Antibody Formation / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D015152:Blotting, Northern; D002648:Child; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000276:immunology; D007376:Interleukin-2 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D014066:Palatine Tonsil / Q000166:cytology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000032:analysis; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology
D000888:Antibodies, Anti-Idiotypic; D007075:Immunoglobulin M; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D007073:Immunoglobulin E; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin