title: The adaptor protein Shc plays a key role during early B cell development.
abstract: 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.
authors.affiliation: Carter Immunology Center and Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Amber J
authors.initials: AJ
authors.lastname: Giles
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Bender
authors.forename: Kodi S
authors.initials: KS
authors.lastname: Ravichandran
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D018390:Gene Targeting; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D055765:Shc Signaling Adaptor Proteins