Submitted August 29, 2007
Accepted November 15, 2007
Regulation of B cell development by BCAP and CD19 through their binding to phosphoinositide 3-kinase
Yuichi Aiba, Megumi Kameyama, Tetsuo Yamazaki, Thomas F Tedder, and Tomohiro Kurosaki*
Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Yokohama, Ka, Japan
Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguti, Japan
Department of Immunology, Duke University Medical Center, Durham, NC, United States
* Corresponding author; email: kurosaki{at}rcai.riken.jp.
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.
