Regulation of B-cell development by BCAP and CD19 through their binding to phosphoinositide 3-kinase

被引：110

作者：

Aiba, Yuichi ^{[1
]}

Kameyama, Megumi ^{[1
]}

Yamazaki, Tetsuo ^{[2
]}

Tedder, Thomas F. ^{[3
]}

Kurosaki, Tomohiro ^{[1
,2
]}

机构：

[1] RIKEN, Res Ctr Allergy & Immunol, Lab Lymphocyte Differentiat, Yokohama, Kanagawa 2300045, Japan

[2] Kansai Med Univ, Inst Liver Res, Dept Mol Genet, Moriguchi, Osaka, Japan

[3] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27706 USA

来源：

BLOOD | 2008年 / 111卷 / 03期

关键词：

D O I：

10.1182/blood-2007-08-109769

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1497 / 1503

页数：7

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