Bruton's Tyrosine Kinase and Phospholipase Cγ2 Mediate Chemokine-Controlled B Cell Migration and Homing

Control of integrin-mediated adhesion and migration by chemokines plays a critical role in B cell development, differentiation, and function; however, the underlying signaling mechanisms are poorly defined. Here we show that the chemokine SDF-1 induced activation of Bruton's tyrosine kinase (Btk) and that integrin-mediated adhesion and migration in response to SDF-1 or CXCL13, as well as in vivo homing to lymphoid organs, was impaired in Btk-deficient (pre-)B cells. Furthermore, SDF-1 induced tyrosine phosphorylation of Phospholipase Cγ2 (PLCγ2), which, unlike activation of the migration regulatory GTPases Rac or Rap1, was mediated by Btk. PLCγ2-deficient B cells also exhibited impaired SDF-1-controlled migration. These results reveal that Btk and PLCγ2 mediate chemokine-controlled migration, thereby providing insights into the control of B cell homeostasis, trafficking, and function, as well as into the pathogenesis of the immunodeficiency disease X-linked agammaglobulinemia (XLA).