Compensation between Vav-1 and Vav-2 in B cell development and antigen receptor signaling
- 1 June 2001
- journal article
- Published by Springer Nature in Nature Immunology
- Vol. 2 (6) , 548-555
- https://doi.org/10.1038/88756
Abstract
Vav-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-independent 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.Keywords
This publication has 55 references indexed in Scilit:
- Xid -Like Immunodeficiency in Mice with Disruption of the p85α Subunit of Phosphoinositide 3-KinaseScience, 1999
- BLNKImmunity, 1998
- Vav is a regulator of cytoskeletal reorganization mediated by the T-cell receptorCurrent Biology, 1998
- Identification of Two Tyrosine Phosphoproteins, pp70 and pp68, Which Interact with Phospholipase Cγ, Grb2, and Vav after B Cell Antigen Receptor ActivationPublished by Elsevier ,1997
- The CD19–CD21 Complex Regulates Signal Transduction Thresholds Governing Humoral Immunity and AutoimmunityImmunity, 1997
- Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene productNature, 1997
- The SCID but Not the RAG-2 Gene Product Is Required for Sμ–Sε Heavy Chain Class SwitchingImmunity, 1996
- Defective B cell development and function in Btk-deficient miceImmunity, 1995
- Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endotheliumNature, 1995
- Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogeneCell, 1991