Survival of resting mature B lymphocytes depends on BCR signaling via the Igα/β heterodimer
Survival of resting mature B lymphocytes depends on BCR signaling via the Igα/β heterodimer
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DOI：
10.1016/j.cell.2004.05.014
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发表时间：
2004-06-11
期刊：
影响因子：
64.5
通讯作者：
Rajewsky, K
中科院分区：
文献类型：
--
作者：
Kraus, M;Alimzhanov, MB;Rajewsky, K
我们之前的研究表明，I型干扰素通过ig重链缺失诱导cre介导的成熟B细胞表面BCR表达的消融可导致这些细胞凋亡。这导致了来自BCR的存活信号对成熟B细胞至关重要的假设。在这里，我们检验了该模型的两个关键假设。首先，我们证明了成熟B细胞在诱导BCR信号模块突变时的损失，但不排除BCR表面表达。其次，我们发现在缺乏干扰素等外源性诱导剂的情况下，细胞也会在BCR失活时丢失，排除了细胞死亡取决于后者先前的细胞激活。动力学数据表明，缺乏bcr的成熟B细胞寿命严重缩短，半衰期为3-6天。综上所述，这些结果表明BCR信号是保持静止成熟B细胞在体内存活所必需的。
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.