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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3247-3254. Prepublished online as a Blood First Edition Paper on January 11, 2005; DOI 10.1182/blood-2004-08-3165. This Article Full Text (PDF) All Versions of this Article: 2004-08-3165v1 105/8/3247    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Diamant, E. Articles by Melamed, D. Search for Related Content PubMed PubMed Citation Articles by Diamant, E. Articles by Melamed, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 17, 2004 Accepted December 24, 2004 CD19 regulates positive selection and maturation in B lymphopoiesis: Lack of CD19 imposes developmental arrest of immature B cells and consequential stimulation of receptor editing Eran Diamant, Zohar Keren, and Doron Melamed* Department of Immunology, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel Department of Immunology, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Rappaport Family Institute for Research in the Medical Sciences, Haifa, Israel * Corresponding author; email: melamedd{at}tx.technion.ac.il. Ligand-independent signals that are produced by the B cell antigen receptor (BCR) confer an important positive selection check-point for immature B cells. Generation of inappropriate signals imposes developmental arrest of immature B cells, although the fate of these cells has not been investigated. Studies have shown that lack of CD19 results in inappropriate signaling. In immunoglobulin transgenic mice, this inappropriate signaling impairs positive selection and stimulates receptor editing. Here we studied the extent and significance of receptor editing in CD19-regulated positive selection of normal, non-transgenic B-lymphopoiesis, using our bone marrow culture system. We found that lack of CD19 resulted in elevated tonic signaling and impaired maturation as revealed by surface marker expression and by functional assays. Immature CD19-/- B cells did not suppress RAG and underwent intensive receptor editing attempts in culture. Finally, in vivo analysis of light chain isotype expression and J utilization in CD19-/- mice validated our in vitro observations. Our results suggest that CD19 has an important function in regulating positive selection and maturation of non-transgenic B cell precursors, and that receptor editing is an important salvage mechanism for immature B cells that fail positive selection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Aiba, M. Kameyama, T. Yamazaki, T. F. Tedder, and T. Kurosaki Regulation of B-cell development by BCAP and CD19 through their binding to phosphoinositide 3-kinase Blood, February 1, 2008; 111(3): 1497 - 1503. [Abstract] [Full Text] [PDF] S. Hillion, M. Dueymes, P. Youinou, and C. Jamin IL-6 Contributes to the Expression of RAGs in Human Mature B Cells J. Immunol., November 15, 2007; 179(10): 6790 - 6798. [Abstract] [Full Text] [PDF] J. K. Lee, S. O. Mathew, S. V. Vaidya, P. R. Kumaresan, and P. A. Mathew CS1 (CRACC, CD319) Induces Proliferation and Autocrine Cytokine Expression on Human B Lymphocytes J. Immunol., October 1, 2007; 179(7): 4672 - 4678. [Abstract] [Full Text] [PDF] L. Verkoczy, B. Duong, P. Skog, D. Ait-Azzouzene, K. Puri, J. L. Vela, and D. Nemazee Basal B Cell Receptor-Directed Phosphatidylinositol 3-Kinase Signaling Turns Off RAGs and Promotes B Cell-Positive Selection J. Immunol., May 15, 2007; 178(10): 6332 - 6341. [Abstract] [Full Text] [PDF] P.-A. Deglesne, N. Chevallier, R. Letestu, F. Baran-Marszak, T. Beitar, C. Salanoubat, L. Sanhes, J. Nataf, C. Roger, N. Varin-Blank, et al. Survival response to B-cell receptor ligation is restricted to progressive chronic lymphocytic leukemia cells irrespective of zap70 expression. Cancer Res., July 15, 2006; 66(14): 7158 - 7166. [Abstract] [Full Text] [PDF] M. C. van Zelm, I. Reisli, M. van der Burg, D. Castano, C. J.M. van Noesel, M. J.D. van Tol, C. Woellner, B. Grimbacher, P. J. Patino, J. J.M. van Dongen, et al. An antibody-deficiency syndrome due to mutations in the CD19 gene. N. Engl. J. Med., May 4, 2006; 354(18): 1901 - 1912. [Abstract] [Full Text] [PDF]

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