Compensation between Vav-1 and Vav-2 in B cell development and antigen receptor signaling.
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.
Tedford
K
K
Abteilung Physiologische Chemie, Universität Ulm, Albert-Einstein-Allee 11, D-89069 Ulm, Germany.
Nitschke
L
L
Girkontaite
I
I
Charlesworth
A
A
Chan
G
G
Sakk
V
V
Barbacid
M
M
Fischer
K D
KD
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D001483:Base Sequence; D020013:Calcium Signaling; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D017931:DNA Primers / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D051567:Proto-Oncogene Proteins c-vav; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism
D018797:Cell Cycle Proteins; D017931:DNA Primers; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011947:Receptors, Antigen, B-Cell; C496619:Vav1 protein, mouse; C490565:Vav2 protein, mouse