Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling

被引:215
作者
Walmsley, MJ
Ooi, SKT
Reynolds, LF
Smith, SH
Ruf, S
Mathiot, A
Vanes, L
Williams, DA
Cancro, MP
Tybulewicz, VLJ
机构
[1] Natl Inst Med Res, Div Immune Cell Biol, London NW7 1AA, England
[2] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[3] Cincinnati Childrens Hosp Res Fdn, Div Expt Hematol, Cincinnati, OH 45229 USA
关键词
D O I
10.1126/science.1089709
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Rac1 guanosine triphosphatase (GTPase) has been implicated in multiple cellular functions, including actin dynamics, proliferation, apoptosis, adhesion, and migration resulting from signaling by multiple receptors, including the B cell antigen receptor (BCR). We used conditional gene targeting to generate mice with specific Rac1 deficiency in the B cell lineage. In the absence of both Rac1 and the highly related Rac2, B cell development was almost completely blocked. Both GTPases were required to transduce BCR signals leading to proliferation, survival and upregulation of BAFF-R, a receptor for BAFF, a key survival molecule required for B cell development and maintenance.
引用
收藏
页码:459 / 462
页数:4
相关论文
共 26 条
[1]   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
[2]   Toll-like receptor 2-mediated NF-κB activation requires a RacI-dependent pathway [J].
Arbibe, L ;
Mira, JP ;
Teusch, N ;
Kline, L ;
Guha, M ;
Mackman, N ;
Godowski, PJ ;
Ulevitch, RJ ;
Knaus, UG .
NATURE IMMUNOLOGY, 2000, 1 (06) :533-540
[3]   The Rac2 guanosine triphosphatase regulates B lymphocyte antigen receptor responses and chemotaxis and is required for establishment of B-1a and marginal zone B lymphocytes [J].
Croker, BA ;
Tarlinton, DM ;
Cluse, LA ;
Tuxen, AJ ;
Light, A ;
Yang, FC ;
Williams, DA ;
Roberts, AW .
JOURNAL OF IMMUNOLOGY, 2002, 168 (07) :3376-3386
[4]   Rho GTPases in cell biology [J].
Etienne-Manneville, S ;
Hall, A .
NATURE, 2002, 420 (6916) :629-635
[5]   Activation of Rac-1 Rac-2, and Cdc42 by hemopoietic growth factors or cross-linking of the B-lymphocyte receptor for antigen [J].
Grill, B ;
Schrader, JW .
BLOOD, 2002, 100 (09) :3183-3192
[6]   Development and function of B-1 cells - Commentary [J].
Hayakawa, K ;
Hardy, RR .
CURRENT OPINION IN IMMUNOLOGY, 2000, 12 (03) :346-353
[7]   Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation [J].
Inabe, K ;
Ishiai, M ;
Scharenberg, AM ;
Freshney, N ;
Downward, J ;
Kurosaki, T .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (02) :189-200
[8]   Protein kinase B regulates T lymphocyte survival, nuclear factor κB activation, and Bcl-XL levels in vivo [J].
Jones, RG ;
Parsons, M ;
Bonnard, M ;
Chan, VSF ;
Yeh, WC ;
Woodgett, JR ;
Ohashi, PS .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (10) :1721-1733
[9]  
Lentz VM, 1998, J IMMUNOL, V160, P3743
[10]   B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signals [J].
Loder, F ;
Mutschler, B ;
Ray, RJ ;
Paige, CJ ;
Sideras, P ;
Torres, R ;
Lamers, MC ;
Carsetti, R .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (01) :75-89