Lymphokine dependence of STAT3 activation produced by surface immunoglobulin cross-linking and by phorbol ester plus calcium ionophore treatment in Bcells

Stimulation of B cells by surface immunoglobulin (sIg) triggering, or throu gh the mitogenic combination of phorbol eater and calcium ionophore, is acc ompanied by activation of STAT transcription factors. The mechanism respons ible for the delayed nuclear accumulation of phosphorylated STAT3 was exami ned in detail, focusing on the role of B cell-derived lymphokines. sig-indu ced activation of STAT3 was partially inhibited in B cells obtained from IL -6- or IL-10-deficient mice, and was partially blocked by neutralizing anti bodies directed against either of these lymphokines. sig-induced STAT3 acti vation was completely inhibited by combining IL-6- and IL-10-specific neutr alizing antibodies, or by adding individual neutralizing antibodies to B ce lls obtained from lymphokine-deficient animals. In contrast, IL-10 alone ap peared to account for STAT3 activation resulting from B cell stimulation wi th phorbol ester and calcium ionophore. In keeping with these results, solu ble IL-6 and IL-10 were found in supernatant fluid obtained from stimulated B cells. This work indicates that a lymphokine pathway is responsible for STAT3 activation that occurs late after B cell stimulation, and points out differences in B cell activation that result from stimulation through the a ntigen receptor and through pharmacological mimicry of signaling mediators.