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.
D000818:Animals; D000921:Antibody-Producing Cells / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D010703:Phorbol Esters; D010704:Phorbols; D015240:Phorbol 12,13-Dibutyrate; D013755:Tetradecanoylphorbol Acetate