A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-γ2

Abstract

Defects in the gene encoding Bruton's tyrosine kinase (Btk) result in a disease called X-linked agammaglobulinemia, in which there is a profound decrease of mature B cells due to a block in B cell development. Recent studies have shown that Btk is tyrosine phosphorylated and activated upon B cell antigen receptor (BCR) stimulation. To elucidate the functions of this kinase, we examined BCR signaling of DT40 B cells deficient in Btk. Tyrosine phosphorylation of phospholipase C (PLC)-γ2 upon receptor stimulation was significantly reduced in the mutant cells, leading to the loss of both BCR- coupled phosphatidylinositol hydrolysis and calcium mobilization. Pleckstrin homology and Src-homology 2 domains of Btk were required for PLC-γ2 activation. Since Syk is also required for the BCR-induced PLC-γ2 activation, our findings indicate that PLC-γ2 activation is regulated by Btk and Syk through their concerted actions.