IL-4 and transforming growth factor-β suppress human immunoglobulin secretion in vitro by surface IgD− B cells

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Abstract
SUMMARY: The effect of IL-4 and transforming growth factor-β (TGF-β) on immunogiobulin 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 interferongamma (IFN-γ) to the cultures. We also showed that TGF-β suppressed the immunoglobulin secretion by purified B cells activated by EL4 cells and PMA. To investigate whether IL-4 or TGF-β 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-β. Such activated B cells secreted large quantities of IgG1, IgG2, IgG3, IgA1, IgA2 and IgM, and IL-4 and TGF-β suppressed all these isotypes by >80%. The data demonstrated that IL-4 and TGF-β 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-β acted directly on isolated B cells.