Vav proteins regulate peripheral B-cell survival.
Mice lacking all 3 Vav proteins fail to produce significant numbers of recirculating follicular or marginal zone B cells. Those B cells that do mature have shortened lifespans. The constitutive nuclear factor-kappaB (NF-kappaB) activity of resting naive B cells required Vav function and expression of cellular reticuloendotheliosis (c-Rel). Rel-A was reduced in Vav-deficient B cells. Furthermore, expression of the NF-kappaB-regulated antiapoptotic genes A1 and Bcl-2 was reduced in mature Vav-deficient B cells. Overexpression of Bcl-2 restored the number of mature follicular B cells in the spleens of Vav-deficient mice. When activated by B-cell receptor (BCR) cross-linking, Vav-deficient B cells failed to activate NF-kappaB. Vav proteins thus regulate an NF-kappaB-dependent survival signal in naive B cells and are required for NF-kappaB function after BCR cross-linking.
Vigorito
Elena
E
Laboratory of Lymphocyte Signaling and Development, Molecular Immunology Programme, The Babraham Institute, Babraham, Cambridge CB2 4AT, United Kingdom. elena.vigorito@bbsrc.ac.uk
Gambardella
Laure
L
Colucci
Francesco
F
McAdam
Simon
S
Turner
Martin
M
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival; D004396:Coloring Agents / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D015536:Down-Regulation; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D019076:Transgenes
D004396:Coloring Agents; D003432:Cross-Linking Reagents; D020662:Guanine Nucleotide Exchange Factors; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D020569:Proto-Oncogene Proteins c-rel; D051567:Proto-Oncogene Proteins c-vav; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D051996:Transcription Factor RelA; C490565:Vav2 protein, mouse; C496622:Vav3 protein, mouse; D001973:Bromodeoxyuridine