Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Apoptosis
-
B-Lymphocytes / cytology*
-
Blotting, Western
-
Bone Marrow Cells / cytology
-
Bromodeoxyuridine / pharmacology
-
Cell Nucleus / metabolism
-
Cell Proliferation
-
Cell Separation
-
Cell Survival
-
Coloring Agents / pharmacology
-
Cross-Linking Reagents / pharmacology
-
Down-Regulation
-
Flow Cytometry
-
Gene Expression Regulation*
-
Guanine Nucleotide Exchange Factors / genetics
-
Guanine Nucleotide Exchange Factors / physiology*
-
Mice
-
Mutation
-
NF-kappa B / metabolism*
-
Proto-Oncogene Proteins c-bcl-2 / metabolism
-
Proto-Oncogene Proteins c-rel / metabolism
-
Proto-Oncogene Proteins c-vav / genetics
-
Proto-Oncogene Proteins c-vav / physiology*
-
Receptors, Antigen, B-Cell / metabolism
-
Recombinant Fusion Proteins / metabolism
-
Signal Transduction
-
Spleen / cytology
-
Time Factors
-
Transcription Factor RelA / metabolism
-
Transgenes
Substances
-
Coloring Agents
-
Cross-Linking Reagents
-
Guanine Nucleotide Exchange Factors
-
NF-kappa B
-
Proto-Oncogene Proteins c-bcl-2
-
Proto-Oncogene Proteins c-rel
-
Proto-Oncogene Proteins c-vav
-
Receptors, Antigen, B-Cell
-
Recombinant Fusion Proteins
-
Transcription Factor RelA
-
Vav2 protein, mouse
-
Vav3 protein, mouse
-
Bromodeoxyuridine