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Science 17 October 2003:
Vol. 302. no. 5644, pp. 459 - 462
DOI: 10.1126/science.1089709
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Reports

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{dagger}

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.

1 Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK.
2 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
3 Division of Experimental Hematology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: vtybule{at}nimr.mrc.ac.uk

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