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

Y Aiba, M Kameyama, T Yamazaki… - Blood, The Journal …, 2008 - ashpublications.org
Y Aiba, M Kameyama, T Yamazaki, TF Tedder, T Kurosaki
Blood, The Journal of the American Society of Hematology, 2008ashpublications.org
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 …
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.
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