Inhibitors of protein tyrosine kinases and protein tyrosine phosphatases suppress IL-4-induced CD23 expression and release by human B lymphocytes.

The pleiotropic lymphokine IL-4 is a growth and differentiation factor for human B cells. IL-4 induces the expression of the CD23 (Fc epsilon RII) molecule on B lymphocytes and promotes the release of its soluble form (sCD23); the cleavage fragments of the latter have been reported to modulate IL-4-dependent IgE biosynthesis. In the present work, we have tested the effects of inhibitors of protein tyrosine kinases (PTK) and protein phosphatases (PP) on the induction by IL-4 of the membrane and soluble forms of CD23. The PTK inhibitors genistein and lavendustin A were found to suppress, in a dose-dependent way, the induction by IL-4 of CD23 membrane expression as well as CD23 release by resting and SAC-preactivated B lymphocytes. No such suppression was detected with inhibitors of serine and threonine kinases. The addition of the protein tyrosine phosphatase (PTP) inhibitor sodium orthovanadate also resulted in a marked decrease in CD23 induction by IL-4. Cell viability was little affected by these inhibitors. However, a diminution of the large activated B cell population was observed, which correlated with an inhibition of the entry in the S phase. Partial inhibition of sCD23 release was also observed with okadaic acid and calyculin A, two inhibitors of serine/threonine PP, but only at concentrations which block PP1 in addition to PP2A. These results suggest that protein tyrosine phosphorylation and dephosphorylation may play a major role in IL-4 signalling. This conclusion was strengthened by the observation that a mAb anti-CD45, a membrane tyrosine phosphatase, inhibited IL-4-induced sCD23 release by B lymphocytes.