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Published online October 14, 2009
The Journal of Immunology, 2009, 183, 5468 -5476
Copyright © 2009 by The American Association of Immunologists, Inc.
doi:10.4049/jimmunol.0902344
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The Adaptor Protein Shc Plays a Key Role during Early B Cell Development1

Amber J. Giles, Timothy P. Bender, and Kodi S. Ravichandran2

Carter Immunology Center and Department of Microbiology, University of Virginia, Charlottesville, VA 22908

The adaptor protein Shc is phosphorylated downstream of many cell surface receptors, including Ag and cytokine receptors. However, the role of Shc in B cell development has not been addressed. Here, through conditional expression of a dominant negative Shc mutant and conditional loss of Shc protein expression, we tested a role for Shc during early B lymphopoiesis. We identified a requirement for Shc beginning at the transition from the pre-pro-B to pro-B stage, with a strong reduction in the number of pre-B cells. This developmental defect is due to increased cell death rather than impaired proliferation or commitment to the B lineage. Additional studies suggest a role for Shc in IL-7-dependent signaling in pro-B cells. Shc is phosphorylated in response to IL-7 stimulation in pro-B cells, and pro-B cells from mice with impaired Shc signaling display increased apoptosis. Together, these data demonstrate a critical role for Shc in early B lymphopoiesis with a requirement in early B cell survival. In addition, we also identify Shc as a required player in signaling downstream of the IL-7R in early B cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by National Institute of Allergy and Infectious Diseases Grant 2RO1AI43425 (to K.S.R.).

2 Address correspondence and reprint requests to Dr. Kodi S. Ravichandran, Carter Immunology Center, MR-6, Room 3708, 345 Crispell Drive, Charlottesville, VA 22908. E-mail address: ravi{at}virginia.edu

3 Abbreviations used in this paper: CLP, common lymphoid progenitor cell; PI, propidium iodide; ShcWT, wild-type Shc.

4 The online version of this article contains supplemental material.


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The JI 2009 183: 5435-5436. [Full Text]  





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