IL-13 induces proliferation, Ig isotype switching, and Ig synthesis by immature human fetal B cells.
In this study it is demonstrated that the novel T cell-derived cytokine IL-13 induces proliferation, Ig isotype switching, and Ig synthesis by human immature B cells derived from fetal bone marrow (BM). IL-13 induced proliferation and IgM, total IgG, IgG4, and IgE synthesis when total fetal BM cells or highly purified s mu+, CD10+, CD19+ fetal B cells were cultured in the presence of anti-CD40 mAb or activated CD4+ T cells. Although the ratios of the different isotypes produced in response to IL-13 were similar to those induced by IL-4, the levels of Ig produced in response to IL-13 were generally 5- to 15-fold lower, indicating that IL-13 is less potent than IL-4. In addition, in co-cultures of fetal B cells and CD4+ T cell clones IL-13 was effective only in the presence of IL-7, which may be due to the fact that IL-13, in contrast to IL-4, does not act on T cells. IL-13- and IL-4-induced IgE synthesis by s mu+, CD19+ fetal B cells was enhanced by IL-6 and inhibited by IL-12, IFN-alpha, IFN-gamma, and transforming growth factor-beta, suggesting that IL-13 and IL-4 induce IgE synthesis via similar signaling pathways. Like IL-4, IL-13 also induced Ig production, including IgG4 and IgE synthesis, by highly purified s mu-, CD10+, CD19+ pre-B cells co-cultured in the presence of activated cloned CD4+ T cells and IL-7. However, in contrast to IL-4, IL-13 did not enhance CD23, CD40, and HLA-DR expression on cultured s mu- pre-B cells in the absence of other stimuli, suggesting that IL-13 alone does not activate pre-B cells. Taken together, our data indicate that IL-13 induces proliferation, Ig isotype switching, and Ig production by immature fetal B cells in the presence of costimulatory signals provided by activated CD4+ T cells or anti-CD40 mAb. IL-13 is another cytokine that, in addition to IL-4, can induce isotype switching to IgG4 and IgE synthesis in immature human B cells.
Punnonen
J
J
DNAX Research Institute of Molecular and Cellular Biology, Human Immunology Department, Palo Alto, CA 94304.
de Vries
J E
JE
D000917:Antibody Formation / Q000187:drug effects*; D015703:Antigens, CD / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001853:Bone Marrow / Q000196:embryology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000378:metabolism*; D016130:Immunophenotyping; D066298:In Vitro Techniques; D018793:Interleukin-13; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D016207:Cytokines; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D018793:Interleukin-13; D007378:Interleukins; D015847:Interleukin-4; D007073:Immunoglobulin E