Synergistic action of A23187 and phorbol ester on human B cell activation.
We have investigated the existence of a synergy occurring between the calcium ionophore A23187 and phorbol myristic acetate (PMA) with respect to human B cell proliferation and differentiation. The combination of A23187 (250 to 500 nM) with nonmitogenic concentrations of PMA (1 to 3 ng/ml) resulted in a strong proliferative response in human tonsillar, spleen, and peripheral blood B cells. This proliferation could not be blocked by anti-Tac antibody at concentrations that effectively inhibited T cell proliferation under similar culture conditions, suggesting that IL 2 and its receptor are not involved in B cell proliferation in this system. During a 3-day culture period, A23187 (500 nM) did not activate B cells in terms of changes in cell size or in the expression of transferrin receptor, HLA-DR, and Tac antigen. PMA at a nonmitogenic concentration (3 ng/ml) enhanced the expression of the first two markers. Combination of the ionophore with PMA induced the occurrence of Tac and further increased the expression of transferrin receptor and HLA-DR. A23187 similarly enhanced the PMA-mediated increase in cell size. PMA and A23187 did not induce differentiation to lg production. However, when cells were prestimulated with a combination of the two agents and were recultured in the presence of a preparation containing B cell differentiation factor, a strong increase in IgM, IgG, and IgA production was found. We conclude that PMA and A23187 synergistically trigger intracellular events in human B cells, leading to proliferation and to responsiveness to differentiation factors.
D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D014066:Palatine Tonsil / Q000166:cytology; D010704:Phorbols / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007136:Immunoglobulins; D010704:Phorbols; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate