Phorbol esters inhibit murine B cell differentiation to immunoglobulin secretion but not proliferation

Bacterial lipopolysaccharide (LPS) induces resting B cells to proliferate and to secrete IgM. We have found that addition of phorbol esters (PE) such as phorbol myristate acetate (PMA) to murine B cells specifically inhibits LPS-induced IgM secretion but not proliferation. PMA is extremely potent, with half-maximal inhibition occurring at about 10 pM. The effect on B cells appears to be due to interaction with PE receptors, because a series of PE have similar potencies for tumor promotion, binding to receptors, and inhibition of IgM secretion. PE also inhibit IgM secretion induced by T cell-derived lymphokines and LPS-induced IgG secretion. Results of these studies suggest that the protein kinase C, with which PE interact, plays an important role in the regulation of B cell differentiation and may also provide a powerful tool for dissecting molecular events involved in induction of Ig secretion.