IL-4 and transforming growth factor-beta suppress human immunoglobulin secretion in vitro by surface IgD- B cells.
The effect of IL-4 and transforming growth factor-beta (TGF-beta) on immunoglobulin secretion in vitro by peripheral blood mononuclear cells (PBMC) or purified B cells activated with murine EL4 thymoma cells and phorbol myristate acetate (PMA) was investigated. As previously reported, IL-4 induced IgE and IgG4 secretion by B cells in PBMC preparations and B cells activated with EL4 cells and PMA. However, when B cells, either in PBMC preparations or purified and activated with EL4 cells and PMA, spontaneously secreted large quantities of immunoglobulin, IL-4 suppressed the immunoglobulin secretion of all isotypes. IL-4 also suppressed the IgE secretion by B cells from an atopic dermatitis patient. This suppressive effect was not reversed by adding IL-2 or interferon-gamma (IFN-gamma) to the cultures. We also showed that TGF-beta suppressed the immunoglobulin secretion by purified B cells activated by EL4 cells and PMA. To investigate whether IL-4 or TGF-beta suppressed immunoglobulin secretion by in vivo 'switched' and isotype-committed B cells, sIgD- B cells were isolated, activated with EL4 cells and PMA and cultured with IL-4 or TGF-beta. Such activated B cells secreted large quantities of IgG1, IgG2, IgG3, IgA1, IgA2 and IgM, and IL-4 and TGF-beta suppressed all these isotypes by greater than 80%. The data demonstrated that IL-4 and TGF-beta suppress immunoglobulin secretion in vitro by in vivo isotype-committed sIgD- B cells, suggesting that these lymphokines may play a down-regulatory role on differentiated isotype-committed B cells in an isotype-unrestricted manner. The data also showed that IL-4 and TGF-beta acted directly on isolated B cells.
Ninomiya
C
C
Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla.
Spiegelberg
H L
HL
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007072:Immunoglobulin D / Q000032:analysis*; D007132:Immunoglobulin Isotypes / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D011947:Receptors, Antigen, B-Cell / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013945:Thymoma / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007072:Immunoglobulin D; D007132:Immunoglobulin Isotypes; D007136:Immunoglobulins; D007376:Interleukin-2; D011947:Receptors, Antigen, B-Cell; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate