Signal transduction mechanisms of Ia induction in B cells by interleukin 4 and immunoglobulin receptors

Abstract Molecular mechanisms of signal transduction through receptors for interleukin 4 (IL-4) are still largely unknown. To elucidate the second messenger(s) of IL-4 action in mature B cells, we performed blocking experiments with inhibitors of various aspects of cellular responses, using Ia-inducing activity of IL-4 as a readout system. In the event, only agents that are shown to inhibit calcium ion (Ca 2+ ) release from intracellular stores, such as 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8) and ryanodine, could block the IL-4 action in a dose-dependent fashion. These results suggest that the process leading to the final expression of IL-4 action may be mediated, at some point, by the release of Ca 2+ from intracellular stores. In the parallel experiments with antiimmunoglobulin (Ig) antibody, we found that amiloride, an inhibitor of Na + H + pump, blocks the Ia induction by anti-IgM antibody. Thus the Na + H + exchange system activated by anti-Ig antibody may be present in mature B cells.