BCR-mediated apoptosis associated with negative selection of immature B cells is selectively dependent on Pten

B 房间受体(BCR ) 的分子的基础在不成熟的 B 房间的否定选择期间导致了 apoptosis 大部分是未知的。我们使用高度产生导致 BCR 的 apoptosis 证明 Pten 有选择地为 mitochondrial 死亡小径的调停 BCR 的开始被要求的过渡不成熟的 B 房间。明确地，删除 Pten，然而并非另外的 pro-apoptotic 分子，废除得到 BCR 的 apoptosis 并且在野类型的不成熟的 B 房间改进生存能力。我们进一步在不成熟的 B 房间识别生理地并且显著地更高的细胞内部的 Pten 水平，作为与成熟 B 房间相比，它向在不成熟的 B 房间的死亡为低 AKT 活动和倾向负责。用 AKT 的一种组成的形式或到与在成熟 B 房间看那可比较的水平的 Pten 的减小的 AKT 活动的恢复救不成熟的 B 房间免于导致 BCR 的 apoptosis。因此，我们提供 Pten 是导致 BCR 的房间死亡的一个必要调停人，并且细胞内部的 Pten 层次的那条微分规定决定 BCR 结扎是否支持房间死亡或幸存的证据。我们的调查结果提供珍贵卓见进位于否定选择和不成熟的 B 房间的同种细胞的删除下面的机制。

The molecular basis of B cell receptor （BCR）-induced apoptosis during the negative selection of immature B cells is largely unknown. We use transitional immature B cells that are highly susceptible to BCR-induced apoptosis to show that Pten is selectively required for BCR-mediated initiation of the mitochondrial death pathway. Specifically, deleting Pten, but not other pro-apoptotic molecules, abrogates BCR-elicited apoptosis and improves viability in wild-type immature B cells. We further identify a physiologically and significantly higher intracellular Pten level in immature B cells, as compared to mature B cells, which is responsible for low AKT activity and the propensity to- wards death in immature B cells. Restoration of AKT activity using a constitutive form of AKT or reduction of Pten to a level comparable with that seen in mature B cells rescues immature B cells from BCR-induced apoptosis. Thus, we provide evidence that Pten is an essential mediator of BCR-induced cell death, and that differential regulation of intracellular Pten levels determines whether BCR ligation promotes cell death or survival. Our findings provide a valuable insight into the mechanisms underlying negative selection and clonal deletion of immature B cells.