CD19 regulates intrinsic B lymphocyte signal transduction and activation through a novel mechanism of processive amplification
CD19 regulates intrinsic B lymphocyte signal transduction and activation through a novel mechanism of processive amplification
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DOI：
10.1385/ir:22:2-3:281
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发表时间：
2000-01-01
影响因子：
4.4
通讯作者：
Tedder, TF
中科院分区：
文献类型：
--
作者：
Fujimoto, M;Poe, JC;Tedder, TF
B淋巴细胞的命运取决于内在和B细胞抗原受体（BCR）诱导的信号。这些信号被应答调节因子如控制成熟B细胞活化的CD 19解释和修饰。本文综述了目前对CD 19如何调控B淋巴细胞信号传导的认识。首先，CD 19建立了一个新的Src家族激酶放大环，调节静息B细胞的基础信号转导阈值。此外，CD 19在BCR连接后放大Src家族激酶活化。林恩活性的CD 19扩增导致CD 19和下游底物（包括CD 22）的进行性磷酸化。磷酸化的CD 19募集其他效应分子，包括Vav、Grb 2、磷酸肌醇3-激酶、磷脂酶C γ 2和c-Abl，其可能有助于CD 19调节B细胞功能。CD 19/林恩复合物形成还调节CD 22和Fc γ RIIB的磷酸化，其通过募集SHP 1和SHIP磷酸酶抑制B细胞信号转导。这些观察提供了深入了解CD 19如何支配B细胞中转导的信号的分子顺序和强度，以及CD 19表达或信号传导功能的扰动如何有助于自身免疫。
The fate of B lymphocytes is dependent on intrinsic and B cell antigen receptor (BCR)-induced signals. These signals are interpreted and modified by response regulators such as CD19 that govern mature B cell activation. The current understanding of how CD19 governs B lymphocyte signaling is outlined in this review. Primarily, CD19 establishes a novel Src-family kinase amplification loop that regulates basal signal transduction thresholds in resting B cells. Moreover, CD19 amplifies Src-family kinase activation following BCR ligation. CD19 amplification of Lyn activity leads to processive phosphorylation of CD19 and downstream substrates including CD22. Phosphorylated CD19 recruits other effector molecules including Vav, Grb2, phosphoinositide 3-kinase, phospholipase C gamma2, and c-Abl, which may contribute to CD19 regulation of B cell function. CD19/Lyn complex formation also regulates phosphorylation of CD22 and Fc gamma RIIB, which inhibit B cell signal transduction through the recruitment of the SHP1 and SHIP phosphatases. These observations provide insight into how CD19 governs the molecular ordering and intensity of signals transduced in B cells, and how perturbations in CD19 expression or signaling function may contribute to autoimmunity.