Inhibition by phorbol esters of antiimmunoglobulin induced calcium signalling and B‐cell activation

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Abstract
The inhibitory effect of phorbol dibutyrate (PDB) on B‐cell stimulation was evaluated using a model in which activation is induced by modest doses of antiimmunoglobulin antibody (anti‐lg) and progression to DNA synthesis is induced by cytochalasin. PDB preferentially inhibited anti‐lg‐induced activation and did so during brief (2 hr) preincubation with anti‐lg. Activation was inhibited whether PDB was added before or shortly after anti‐lg. Since activation for cytochalasin responsiveness appears to be mediated by Ca2+, the effect of PDB on the anti‐lg‐induced rise in intracellular Ca2+ was evaluated. PDB (and other phorbol esters that activate protein kinase C) inhibited the rise in Ca2+ normally associated with anti‐lg treatment; moreover, PDB reversed an established anti‐lg‐induced Ca2+ response. These data suggest that phorbol esters inhibit B‐cell activation by interfering with the elevated levels of intracellular Ca2+ produced by cross‐linking of surface immunoglobulin by anti‐lg. This could represent a “feedback inhibition” type of response, but it remains to be seen if this occurs under physiological conditions of protein kinase C activation.

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