RRC ID 42031
Author Spaargaren M, Beuling EA, Rurup ML, Meijer HP, Klok MD, Middendorp S, Hendriks RW, Pals ST.
Title The B cell antigen receptor controls integrin activity through Btk and PLCgamma2.
Journal J Exp Med
Abstract Integrin-mediated adhesion and B cell antigen receptor (BCR) signaling play a critical role in B cell development and function, including antigen-specific B cell differentiation. Here we show that the BCR controls integrin alpha4beta1 (VLA-4)-mediated adhesion of B cells to vascular cell adhesion molecule-1 and fibronectin. Molecular dissection of the underlying signaling mechanism by a combined biochemical, pharmacological, and genetic approach demonstrates that this BCR-controlled integrin-mediated adhesion requires the (consecutive) activation of Lyn, Syk, phosphatidylinositol 3-kinase, Bruton's tyrosine kinase (Btk), phospholipase C (PLC)gamma2, IP3R-mediated Ca2+ release, and PKC. In contrast, activation of mitogen-activated protein kinase kinase (MEK) or extracellular signal-regulated kinase (ERK) is not required, and simultaneous activation of MEK, ERK, and PKB is not sufficient either. Furthermore, Btk is also involved in the control of integrin-mediated adhesion of preB cells. The control of integrin alpha4beta1-mediated B cell adhesion by the BCR involves cytoskeletal reorganization and integrin clustering. These results reveal a novel function for the BCR and Btk, i.e., regulation of integrin alpha4beta1 activity, thereby providing new insights into the control of B cell development and differentiation, as well as into the pathogenesis of the immunodeficiency disease X-linked agammaglobulineamia (XLA).
Volume 198(10)
Pages 1539-50
Published 2003-11-17
DOI 10.1084/jem.20011866
PII jem.20011866
PMID 14610042
IF 11.743
Times Cited 134
Human and Animal Cells DT40(RCB1464) Syk^(-) DT40(RCB1470) Btk^(-) DT40(RCB1468) PLC-γ2^(-) DT40(RCB1469)