Regulation of B-cell development by BCAP and CD19 through their binding to phosphoinositide 3-kinase
Regulation of B-cell development by BCAP and CD19 through their binding to phosphoinositide 3-kinase
复制标题
DOI：
10.1182/blood-2007-08-109769
复制
发表时间：
2008-02-01
期刊：
影响因子：
20.3
通讯作者：
Kurosaki, Tomohiro
中科院分区：
文献类型：
--
作者：
Aiba, Yuichi;Kameyama, Megumi;Kurosaki, Tomohiro
尽管磷脂酰肌醇3-激酶（PI 3 K）在B细胞发育中的重要性，但其激活机制仍不清楚。在这项研究中，我们发现，BCAP和CD 19的缺失导致BCR介导的Akt活化几乎完全阻断，并导致未成熟和成熟B细胞生成的严重缺陷。BCAP和CD 19中的YXXM基序对于调节B细胞发育至关重要，因为这些基序的突变消除了它们诱导BCR介导的Akt活化以及促进B细胞发育的能力。此外，CD 19（-/-）BCAP（-/-）B细胞中的发育缺陷通过引入组成型活性形式的PI 3 K或PDK 1而部分缓解。总之，我们的数据表明，BCAP和CD 19在BCR介导的PI 3 K活化中具有互补作用，从而至少部分地促进B细胞发育。
Despite the importance of phosphoinositide 3-kinase (PI3K) in B-cell development, its activation mechanism still remains elusive. In this study, we show that deletion of both BCAP and CD19 leads to an almost complete block of BCR-mediated Akt activation and to severe defects in generation of immature and mature B cells. The YXXM motifs in BCAP and CD19 are crucial for regulating B-cell development in that mutation of these motifs abrogated their ability to induce BCR-mediated Akt activation as well as to promote B-cell development. Furthermore, the developmental defect in CD19(-/-)BCAP(-/-) B cells was partly relieved by introducing a constitutively active form of PI3K or PDK1. Together, our data suggest that BCAP and CD19 have complementary roles in BCR-mediated PI3K activation, thereby, at least in part, contributing to B-cell development.