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Molecular and Cellular Biology, April 2007, p. 3109-3122, Vol. 27, No. 8
0270-7306/07/$08.00+0     doi:10.1128/MCB.01014-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The 3BP2 Adapter Protein Is Required for Optimal B-Cell Activation and Thymus-Independent Type 2 Humoral Response

Grace Chen,^1,2 Ioannis D. Dimitriou,² Jose La Rose,² Subburaj Ilangumaran,³ Wen-Chen Yeh,^4,5, Gina Doody,⁶ Martin Turner,⁶ Jennifer Gommerman,¹ and Robert Rottapel^1,2,5,7,8*

Department of Immunology, University of Toronto, Toronto, Canada,¹ Ontario Cancer Institute, Toronto, Canada M5G 2M9,² University of Sherbrooke, North Sherbrooke, Quebec, Canada J1H 5N4,³ Advanced Medical Discovery Institute, Toronto, Canada M5G 2C1,⁴ Department of Medical Biophysics, University of Toronto, Toronto, Canada,⁵ Lymphocyte Signaling and Development Laboratory, Molecular Immunology Programme, The Babraham Institute, Babraham, Cambridge CB2 4AT, United Kingdom,⁶ Department of Medicine, University of Toronto, Toronto, Canada,⁷ St. Michael's Hospital, 30 Bond St., Toronto, Canada M5B 1W8⁸

Received 6 June 2006/ Returned for modification 6 July 2006/ Accepted 25 January 2007

3BP2 is a pleckstrin homology domain- and Src homology 2 (SH2) domain-containing adapter protein that is mutated in the rare human bone disorder cherubism and which has also been implicated in immunoreceptor signaling. However, a function for this protein has yet to be established. Here we show that mice lacking 3BP2 exhibited a perturbation in the peritoneal B1 and splenic marginal-zone B-cell compartments and diminished thymus-independent type 2 antigen response. 3BP2^–/– B cells demonstrated a proliferation defect in response to antigen receptor cross-linking and a heightened sensitivity to B-cell receptor-induced death via a caspase-3-dependent apoptotic pathway. We show that 3BP2 binds via its SH2 domain to the CD19 signaling complex and is required for optimum Syk phosphorylation and calcium flux.

Published ahead of print on 5 February 2007.

Present address: Amgen San Francisco, 1120 Veterans Boulevard, South San Francisco, CA 94080.