Synergistic augmentative effect of interleukin-10 and CD27/CD70 interactions on B-cell immunoglobulin synthesis.
Interleukin-10 (IL-10) is a potent cytokine that regulates immunoglobulin synthesis by B cells. CD27/CD70 interactions by direct cell-to-cell contact are also needed to produce substantial amounts of immunoglobulin. We have investigated the effects of IL-10 and CD27/CD70 interactions on the immunoglobulin synthesis. In the presence of IL-10 stimulation, the production of IgG, IgM and IgA was increased synergistically by the addition of CD27 ligand (CD70)-transfectants in a dose-dependent manner, which was completely blocked by anti-CD70 monoclonal antibody. In contrast, CD70-transfectants additively enhanced the immunoglobulin production in the presence of IL-2, IL-4, or IL-6. The synergistic enhancement of the immunoglobulin production by IL-10 and CD70-transfectants was remarkable in highly purified CD27+ B cells, but there was no immunoglobulin production in CD27- B cells. Furthermore, by the addition of CD70-transfectants, the synthesis of IgG1, IgG2, IgG3 and IgG4 was also enhanced in the presence of IL-10. On the other hand, IL-10 diminished CD27 expression in B cells. B-cell proliferation was augmented by CD70-transfectants with IL-10 or IL-10 plus IL-2. The addition of IL-2 further augmented the immunoglobulin production which was synergistically enhanced by IL-10 and CD27 triggering. Taken together, the co-operative response to IL-10 and CD27/CD70 interactions regulates B-cell immunoglobulin production.
Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
H
H
Nagumo
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K
Agematsu
D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
D019013:CD40 Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007376:Interleukin-2; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D016753:Interleukin-10; D023201:CD40 Ligand; D015847:Interleukin-4