PI3 Kinase Signals BCR-Dependent Mature B Cell Survival

被引:529
|
作者
Srinivasan, Lakshmi [1 ,2 ]
Sasaki, Yoshiteru [1 ,2 ]
Calado, Dinis Pedro [1 ,2 ]
Zhang, Baochun [1 ,2 ]
Paik, Ji Hye [3 ]
DePinho, Ronald A. [3 ]
Kutok, Jeffrey L. [4 ]
Kearney, John F. [5 ]
Otipoby, Kevin L. [1 ,2 ]
Rajewsky, Klaus [1 ,2 ]
机构
[1] Harvard Univ, Sch Med, Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
[4] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
[5] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA
关键词
NF-KAPPA-B; FOXO TRANSCRIPTION FACTORS; CLASS-SWITCH RECOMBINATION; ANTIGEN RECEPTOR; PHOSPHATIDYLINOSITOL; 3-KINASE; MARGINAL ZONE; POSITIVE SELECTION; CRITICAL ROLES; LYMPHOCYTES; ACTIVATION;
D O I
10.1016/j.cell.2009.08.041
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous work has shown that mature B cells depend upon survival signals delivered to the cells by their antigen receptor (BCR). To identify the molecular nature of this survival signal, we have developed a genetic approach in which ablation of the BCR is combined with the activation of specific, BCR dependent signaling cascades in mature B cells in vivo. Using this system, we provide evidence that the survival of BCR deficient mature B cells can be rescued by a single signaling pathway downstream of the BCR, namely PI3K signaling, with the FOXO1 transcription factor playing a central role.
引用
收藏
页码:573 / 586
页数:14
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