Survival of resting mature B lymphocytes depends on BCR signaling via the Igα/β heterodimer

被引:448
作者
Kraus, M
Alimzhanov, MB
Rajewsky, N
Rajewsky, K
机构
[1] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[3] Univ Cologne, Inst Genet, D-50931 Cologne, Germany
[4] NYU, Dept Biol, New York, NY 10003 USA
关键词
D O I
10.1016/j.cell.2004.05.014
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
We previously showed that type I interferon-induced, Cre-mediated ablation of surface BCR expression in mature B cells through Ig-heavy chain deletion results in apoptosis of these cells. This led to the hypothesis that survival signals from the BCR are vital for mature B cells. Here, we test two critical assumptions of this model. First, we demonstrate loss of mature B cells upon induced mutation of a signaling module of the BCR, not precluding BCR surface expression. Second, we show that the cells are also lost upon BCR inactivation in the absence of an exogenous inducer like interferon, excluding that cell death depends on previous cellular activation by the latter. Kinetic data demonstrate that BCR-less mature B cells have a severely reduced lifespan, with a half-life of 3-6 days. Together these results establish that BCR signaling is required to keep resting mature B cells alive in vivo.
引用
收藏
页码:787 / 800
页数:14
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