Nature Immunology
2, 548 - 555 (2001)
doi:10.1038/88756
Compensation between Vav-1 and Vav-2 in B cell development and antigen receptor signalingKerry Tedford1, 2, Lars Nitschke3, Irute Girkontaite1, Amanda Charlesworth4, Gordon Chan1, 2, Vadim Sakk1, Mariano Barbacid5
& Klaus-Dieter Fischer11
Abteilung Physiologische Chemie, Universität Ulm, Albert-Einstein-Allee 11, D-89069 Ulm, Germany. 2
Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), Universität Würzburg, Versbacher Strasse 5, D-97078 Würzburg, Germany. 3
Institut für Virologie und Immunobiologie, Universität Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany. 4
Department of Medicine, University of Chicago, Chicago, IL 60637, USA. 5
M. Barbacid Centro Nacional de Investigaciones Oncologicas Carlos III, 28220 Majadahonda, Madrid, Spain.
Correspondence should be addressed to Klaus-Dieter Fischer klaus.fischer@medizin.uni-ulm.deVav-1 and Vav-2 are closely related Dbl-homology GTP exchange factors (GEFs) for Rho GTPases. Mutation of Vav-1 disrupts T cell development and T cell antigen receptor−induced activation, but has comparatively little effect on B cells. We found that combined deletion of both Vav-1 and Vav-2 in mice resulted in a marked reduction in mature B lymphocyte numbers. Vav-1-/-Vav-2-/- B cells were unresponsive to B cell antigen receptor (BCR)-driven proliferation in vitro and to thymus-indepen-dent antigen in vivo. BCR-stimulated intracellular calcium mobilization was greatly impaired in Vav-1-/-Vav-2-/- B cells. These findings establish a role for Vav-2 in BCR calcium signaling and reveal that the Vav family of GEFs is critical to B cell development and function.
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