bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice.
bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice.
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DOI：
10.1084/jem.183.2.381
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发表时间：
1996-02-01
期刊：
影响因子：
--
通讯作者：
Nunez G
中科院分区：
文献类型：
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作者：
Grillot DA;Merino R;Pena JC;Fanslow WC;Finkelman FD;Thompson CB;Nunez G
我们评估了在B细胞发育过程中，bcl-x的调控和功能，bcl-x是凋亡调节基因家族的成员之一。我们发现Bcl-xL是bcl-x的产物，在B细胞前表达，但在B细胞发育的未成熟和成熟阶段下调。Bcl-xL而非Bcl-2可通过表面免疫球蛋白M （IgM）交联、CD40信号传导或LPS刺激在外周B细胞中迅速诱导。在B细胞谱系中过表达Bcl- xL的转基因小鼠在淋巴器官中表现出明显的外周血B细胞积累，并提高了发育和成熟B细胞的存活率。同时表达bcl-xL和bcl-2基因可进一步提高B细胞存活率。这些研究表明Bcl-2和Bcl-xL在B细胞发育和成熟B细胞活化过程中受到不同的调控。通过表面IgM和CD40信号传导后，Bcl-xL的诱导似乎为成熟B细胞提供了一种额外的保护机制，以对抗与抗原诱导的活化和增殖相关的凋亡信号。
We have assessed during B cell development, the regulation and function of bcl-x, a member of the bcl-2 family of apoptosis regulatory genes. Here we show that Bcl-xL, a product of bcl-x, is expressed in pre-B cells but downregulated at the immature and mature stages of B cell development. Bcl-xL but not Bcl-2 is rapidly induced in peripheral B cells upon surface immunoglobulin M (IgM) cross-linking, CD40 signaling, or LPS stimulation. Transgenic mice that overexpressed Bcl- xL within the B cell lineage exhibited marked accumulation of peripheral B cells in lymphoid organs and enhanced survival of developing and mature B cells. B cell survival was further increased by simultaneous expression of bcl-xL and bcl-2 transgenes. These studies demonstrate that Bcl-2 and Bcl-xL are regulated differentially during B cell development and activation of mature B cells. Induction of Bcl-xL after signaling through surface IgM and CD40 appears to provide mature B cells with an additional protective mechanism against apoptotic signals associated with antigen-induced activation and proliferation.