Intracellular Induction Pathways for CD23 Antigen and Surface Immunoglobulins in Human Tonsillar B Cells: The Roles of Protein Kinase C and Tyrosine Kinaxe-Mediated Signals

The expression of CD23 on human tonsillar B cells is increased following treatment with interleukin 4 (IL-4) or 12-O-tetradecanoylphorbol 13-acetate (TPA), while that of surface immunoglobulins (sIgs) is increased by IL-4 but decreased by TPA. This suggests that the signaling by these effectors may result from distinct second messenger-generating systems. In this study, we attempted to elucidate the signal transduction pathways responsible for the expression of CD23 and sIgs by using different protein kinase C (PKC) and tyrosine kinase (TK) inhibitors. Our results showed that B cells expressed varying amounts of sIgs depending on different activators and inhibitors. Sphingosine, a PKC inhibitor, almost completely reversed the TPA-induced decrease in sIgM and sIgD expression. Other PKC inhibitors, e.g., H7 and staurosporine, had similar but less profound effects. In comparison, the up-regulation of CD23 by IL-4 and TPA was only partially blocked by these PKC inhibitors. TK inhibitors, such as herbimycin A and genistein, decreased both the IL-4- and TPA-induced CD23 expression by 50-80%, but had modest effects on sIgs expression. These findings indicate that CD23 and sIgs expression is regulated by independent pathways: PKC is important for the regulation of sIgs expression while the signals through TK pathways might play the major role in CD23 expression.