Phorbol myristate acetate inhibits anti-IgM-mediated signaling in resting B cells.
Cross-linking the membrane immunoglobulins of resting B cells leads to activation as judged by increased inositol phospholipid metabolism, intracellular free calcium concentration ([Ca2+]i), and cell volume. Such activated B cells enter S phase in the presence of B-cell stimulatory factor 1. Phorbol myristate acetate (PMA) is a potent inhibitor of anti-IgM- and anti-IgD-stimulated B-cell responses. In B cells concentrations of PMA ranging from 0.1 to 100 ng/ml completely inhibit anti-IgM-stimulated DNA synthesis and block anti-IgM-stimulated increases in inositol phospholipid metabolism and in [Ca2+]i. Preincubation periods as short as 4 min block these effects although longer preincubations are somewhat more effective in inhibiting increases in [Ca2+]i. Preincubation with PMA for 1.5 hr does not diminish expression of membrane IgM. This strongly suggests that PMA inhibits responses of resting B cells to anti-IgM by interrupting signal transmission rather than by diminishing cross-linking of membrane immunoglobulin on B cells. In contrast to resting B cells, B cells activated in vitro for 29 hr show enhanced responses to anti-IgM in the presence of PMA.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002462:Cell Membrane / Q000276:immunology; D005260:Female; D007072:Immunoglobulin D / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D010704:Phorbols / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D000888:Antibodies, Anti-Idiotypic; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D010704:Phorbols; D010716:Phosphatidylinositols; D011947:Receptors, Antigen, B-Cell; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium