Critical Roles for Rac1 and Rac2 GTPases in B Cell Development and Signaling
Marita J. Walmsley,1* Steen K. T. Ooi,1* Lucinda F. Reynolds,1 Susan Harless Smith,2 Sandra Ruf,1 Anne Mathiot,1 Lesley Vanes,1 David A. Williams,3 Michael P. Cancro,2 Victor L. J. Tybulewicz1
The Rac1 guanosine triphosphatase (GTPase) has been implicated in multiple cellular functions, including actin dynamics, proliferation, apoptosis, adhesion, and migration resulting from signaling by multiple receptors, including the B cell antigen receptor (BCR). We used conditional gene targeting to generate mice with specific Rac1 deficiency in the B cell lineage. In the absence of both Rac1 and the highly related Rac2, B cell development was almost completely blocked. Both GTPases were required to transduce BCR signals leading to proliferation, survival and up-regulation of BAFF-R, a receptor for BAFF, a key survival molecule required for B cell development and maintenance.
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