Journal
JOURNAL OF IMMUNOLOGY
Volume 183, Issue 9, Pages 5468-5476Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0902344
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- National Institute of Allergy and Infectious Diseases [2RO1AI43425]
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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 She during early B lymphopoiesis. We identified a requirement for She 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 She signaling display increased apoptosis. Together, these data demonstrate a critical role for She in early B lymphopoiesis with a requirement in early B cell survival. In addition, we also identify She as a required player in signaling downstream of the IL-7R in early B cells. The Journal of Immunology, 2009, 183: 5468-5476.
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