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Defining the Requirement for ShcA in Murine B Cell Development

Giles, Amber Jin
Thesis/Dissertation; Online
Giles, Amber Jin
Ravichandran, Kodi
Bender, Timothy
Erickson, Loren
Lorenz, Ulrike
Parsons, Sarah
Taylor, Ronald
The adaptor protein Shc is phosphorylated downstream of many cell surface receptors, including antigen 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, I tested a role for Shc during early B lymphopoiesis. In chapter III, I identified a requirement for Shc beginning at either the transition from the pre-pro-B to pro-B stage or within the pro-B pool, with a strong reduction in the number of pre-B cells. This developmental defect appeared to be due to increased cell death rather than impaired proliferation. Additional studies in chapter IV 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 signs of increased apoptosis. Together, these data suggest a critical role for Shc in early B lymphopoiesis with a requirement in early B cell survival. In addition, I also identify Shc as a required player in signaling downstream of the IL-7 receptor in early B cells. Note: Abstract extracted from PDF text
University of Virginia, Department of Microbiology, PHD, 2009
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