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

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Aiba Y,Kameyama M,Yamazaki T,Tedder TF,Kurosaki T

doi

10.1182/blood-2007-08-109769

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

1497-503

issue

3

eissn

0006-4971

issn

1528-0020

pii

blood-2007-08-109769

journal_volume

111

pub_type

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