Vav proteins regulate peripheral B-cell survival

被引:42
作者
Vigorito, E [1 ]
Gambardella, L [1 ]
Colucci, F [1 ]
McAdam, S [1 ]
Turner, M [1 ]
机构
[1] Babraham Inst, Lab Lymphocyte Signaling & Dev, Mol Immunol Programme, Cambridge CB2 4AT, England
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
D O I
10.1182/blood-2004-12-4894
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Mice lacking all 3 Vav proteins fall 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-kappa B) 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-kappa B-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-kappa B. Vav proteins thus regulate an NF-kappa B-dependent survival signal in naive B cells and are required for NF-kappa B function after BCR cross-linking.
引用
收藏
页码:2391 / 2398
页数:8
相关论文
共 64 条
[1]   Resolution of three nonproliferative immature splenic B cell subsets reveals multiple selection points during peripheral B cell maturation [J].
Allman, D ;
Lindsley, RC ;
DeMuth, W ;
Rudd, K ;
Shinton, SA ;
Hardy, RR .
JOURNAL OF IMMUNOLOGY, 2001, 167 (12) :6834-6840
[2]   Enforced bcl-xL gene expression restored splenic B lymphocyte development in BAFF-R mutant mice [J].
Amanna, IJ ;
Dingwall, JP ;
Hayes, CE .
JOURNAL OF IMMUNOLOGY, 2003, 170 (09) :4593-4600
[3]   PLCγ2 regulates Bcl-2 levels and is required for survival rather than differentiation of marginal zone and follicular B cells [J].
Bell, SE ;
Vigorito, E ;
McAdam, S ;
Reynolds, HM ;
Caraux, A ;
Colucci, F ;
Turner, M .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2004, 34 (08) :2237-2247
[4]  
Borggrefe T, 2001, EUR J IMMUNOL, V31, P2467, DOI 10.1002/1521-4141(200108)31:8<2467::AID-IMMU2467>3.0.CO
[5]  
2-P
[6]   BAFF-induced NEMO-independent processing of NF-κB2 in maturing B cells [J].
Claudio, E ;
Brown, K ;
Park, S ;
Wang, HS ;
Siebenlist, U .
NATURE IMMUNOLOGY, 2002, 3 (10) :958-965
[7]  
Colucci F, 1999, J IMMUNOL, V162, P2761
[8]   Calcium oscillations increase the efficiency and specificity of gene expression [J].
Dolmetsch, RE ;
Xu, KL ;
Lewis, RS .
NATURE, 1998, 392 (6679) :933-936
[9]   Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes [J].
Doody, GM ;
Billadeau, DD ;
Clayton, E ;
Hutchings, A ;
Berland, R ;
McAdam, S ;
Leibson, PJ ;
Turner, M .
EMBO JOURNAL, 2000, 19 (22) :6173-6184
[10]   Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation [J].
Doody, GM ;
Bell, SE ;
Vigorito, E ;
Clayton, E ;
McAdam, S ;
Tooze, R ;
Fernandes, C ;
Lee, IJ ;
Turner, M .
NATURE IMMUNOLOGY, 2001, 2 (06) :542-547