The adaptor protein Shc plays a key role during early B cell development

J Immunol. 2009 Nov 1;183(9):5468-76. doi: 10.4049/jimmunol.0902344. Epub 2009 Oct 14.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Gene Targeting
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Mutation
  • Precursor Cells, B-Lymphoid / cytology*
  • Precursor Cells, B-Lymphoid / immunology
  • Precursor Cells, B-Lymphoid / metabolism*
  • Shc Signaling Adaptor Proteins / biosynthesis
  • Shc Signaling Adaptor Proteins / deficiency
  • Shc Signaling Adaptor Proteins / genetics
  • Shc Signaling Adaptor Proteins / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Stem Cells / cytology
  • Stem Cells / immunology
  • Stem Cells / metabolism

Substances

  • Shc Signaling Adaptor Proteins