Bruton's Tyrosine Kinase and Phospholipase Cgamma2 Mediate Chemokine-Controlled B Cell Migration and Homing

Immunity. 2007 Jan;26(1):93-104. doi: 10.1016/j.immuni.2006.11.012.

Abstract

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 Cgamma2 (PLCgamma2), which, unlike activation of the migration regulatory GTPases Rac or Rap1, was mediated by Btk. PLCgamma2-deficient B cells also exhibited impaired SDF-1-controlled migration. These results reveal that Btk and PLCgamma2 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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Cell Adhesion / immunology
  • Chemokine CXCL12
  • Chemokine CXCL13
  • Chemokines / immunology*
  • Chemokines, CXC / immunology
  • Chemokines, CXC / metabolism
  • Chemotaxis, Leukocyte / immunology*
  • Enzyme Activation / immunology
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Integrins / immunology
  • Integrins / metabolism
  • Mice
  • Phospholipase C gamma / immunology
  • Phospholipase C gamma / metabolism*
  • Protein-Tyrosine Kinases / immunology
  • Protein-Tyrosine Kinases / metabolism*

Substances

  • CXCL12 protein, human
  • CXCL13 protein, human
  • Chemokine CXCL12
  • Chemokine CXCL13
  • Chemokines
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Integrins
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Btk protein, mouse
  • Phospholipase C gamma