Abstract
Antigen receptors on B lymphocytes (BCRs) play a central role in immune regulation by transmitting signals that regulate B lymphocyte survival, growth, and differentiation. Among a number of signaling pathways, the importance of phospholipase C (PLC)-γ2 pathway has been recently underscored by gene targeting experiments in mice. PLC-γ2 activation leads to hydrolysis of phospholipids, yielding IP3 and diacylglycerol (DAG). IP3 binds IP3 receptors located in the endoplasmic reticulum (ER), leading to calcium release from internal stores. Triple knock-out of three IP3 receptor isoforms in DT40 B cells abolishes the BCR-induced calcium mobilization both from internal stores and from extracellular stores, therefore supporting the capacitative calcium entry (CCE) model in which calcium influx channels in the plasma membrane is opened upon depletion of intracellular calcium stores.TRPC1 could be one component of these calcium influx channels in that genetic disruption of TRPC1 significantly attenuates calcium-release-activated calcium currents in DT40 B cells. Moreover, IP3 receptor function is suppressed by loss of TRPC1, suggesting the existence of a functional feed-forward regulatory loop between IP3 receptors and TRPC1 in calcium signaling in B lymphocytes. [Jpn J Physiol 54 Suppl:S47 (2004)]
