Inhibition of interleukin 4‐promoted CD23 production in human B lymphocytes by transforming growth factor‐β, interferons or anti‐CD19 antibody is overriden on engaging CD40

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Abstract
Interleukin 4 (IL4) is an essential component in the sequence of events directing IgE synthesis in uncommitted B lymphocytes. An early consequence of IL4's interaction with the B cell is the induction of CD23, a low‐affinity receptor for IgE (FcϵRII). The present study was designed to explore the detailed regulation of this event. First, we report that transforming growth factor‐β (TGF‐β) is a potent inhibitor of IL4‐promoted CD23 production in human B lymphocytes. The level of inhibition achieved with TGF‐β was greater than that obtained with interferons, or with a monoclonal antibody (mAb) to CD19. Next, we identified three signals, each of which was capable of selectively counteracting the inhibitors of IL 4‐promoted CD23 production: (a) the engagement of surface CD40 antigen with mAb was found to override the influence of all the inhibitors of CD23 expression; (b) mAb to surface IgM overcame the inhibitory actions of TGF‐β and interferons but not that of CD19 ligation; (c) ligation of surface CD72 counteracted the inhibition mediated by TGF‐β but not that generated by interferons or anti‐CD19 antibody. Inhibition of the IL4 signal appeared to be selective for the pathway leading to CD23 induction: none of the inhibitors profoundly altered IL4's ability to enhance surface IgM expression. The study has ramifications for the understanding of events leading to the promotion of IgE synthesis and consolidates the notion of a central role for CD40 in B cell regulation.