TY - JOUR
T1 - Bruton's tyrosine kinase and phospholipase C gamma 2 mediate chemokine-controlled B cell migration and homing
AU - de Gorter, David J. J.
AU - Beuling, Esther A.
AU - Kersseboom, Rogier
AU - Middendorp, Sabine
AU - van Gils, Janine M.
AU - Hendriks, Rudolf W.
AU - Pals, Steven T.
AU - Spaargaren, Marcel
PY - 2007
Y1 - 2007
N2 - 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 C gamma 2 (PLC gamma 2), which, unlike activation of the migration regulatory GTPases Rac or Rap1, was mediated by Btk. PLC gamma 2-deficient B cells also exhibited impaired SDF-1-controlled migration. These results reveal that Btk and PLC gamma 2 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)
AB - 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 C gamma 2 (PLC gamma 2), which, unlike activation of the migration regulatory GTPases Rac or Rap1, was mediated by Btk. PLC gamma 2-deficient B cells also exhibited impaired SDF-1-controlled migration. These results reveal that Btk and PLC gamma 2 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)
U2 - https://doi.org/10.1016/j.immuni.2006.11.012
DO - https://doi.org/10.1016/j.immuni.2006.11.012
M3 - Article
C2 - 17239630
SN - 1074-7613
VL - 26
SP - 93
EP - 104
JO - Immunity
JF - Immunity
IS - 1
ER -