Negative control of store-operated Ca2+ influx by B cell receptor cross-linking

An increase in the intracellular Ca2+ concentration by B cell receptor (BCR ) cross-linking plays important roles in the regulation of B cell functions . [Ca2+](i) is regulated by Ca2+ release from the Ca2+ store as well as sto re-operated Ca2+ influx (SOC). Protein tyrosine kinases downstream of BCR c ross-linking were shown to regulate the mechanism for Ca2+ release. However , it remains elusive whether BCR cross-linking regulates SOC or not. In thi s study, we examined the effect of BCR cross-linking on thapsigargin-induce d SOC in the DT40 B cells. We found that the SOC-mediated increase in intra cellular Ca2+ concentration was inhibited by BCR cross-linking. Using a mem brane-potential-sensitive dye, we found that BCR cross-linking induced depo larization, which is expected to decrease the driving force of Ca2+ influx and SOC channel conductance. When membrane potential was held constant by t he transmembrane K+ concentration gradient in the presence of valinomycin, the BCR-mediated inhibition of SOC was still observed. Thus, the BCR-mediat ed inhibition of SOC involves both depolarization-dependent and depolarizat ion-independent mechanisms of SOC inhibition. The depolarization-independen t inhibition of the SOC was abolished in Lyn-deficient, but not in Bruton's tyrosine kinase-, Syk- or SHIP (Src homology 2 domain containing phosphati dylinositol 5'-phosphatase)-deficient cells, indicating that Lyn is involve d in the inhibition. These results show novel pathways of BCR-mediated SOC regulations.