Redundant and unique regulation of activated mouse B lymphocytes by IL-4 and IL-21.
IL-21 distinctively regulates B cell growth and death, and it redundantly functions with IL-4 for IgG production. B cells likely encounter IL-4 and IL-21 in vivo, as both are secreted by activated T cells. Therefore, the action of both these cytokines was investigated during activation of B cells. IL-21 or the combination of IL-4 and IL-21 inhibited proliferation by purified mouse B cells to LPS or CpG DNA, whereas these cytokines enhanced proliferation after engaging the BCR or CD40. Although B cell subsets expressed somewhat varied levels of the IL-21 receptor, LPS-stimulated follicular and marginal B cell subsets were also dominantly susceptible to IL-21-induced growth arrest and cell death. After activation of B cells with CD40 and LPS, IL-4 and IL-21 distinctively regulated the expression of CD23, CD44, and CD138, and they cooperatively promoted IgG1 class-switching and synthesis. These findings support a model in which the presence of IL-4 and IL-21 inhibits B cells activated by polyclonal innate signals, and they promote B cell expansion and differentiation during T cell-dependent antibody responses, although the individual responses to IL-4 and IL-21 do not always overlap.
Jin
Haoli
H
Department of Microbiology and Immunology, University of Miami School of Medicine, P.O. Box 016960, Miami, FL 33101, USA.
Malek
Thomas R
TR
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000098546:Interleukin-21
D015703:Antigens, CD; D007074:Immunoglobulin G; D007378:Interleukins; D015847:Interleukin-4; D000098546:Interleukin-21