Modulation of IL-7 thresholds by SOCS proteins in developing B lineage cells

J Immunol. 2011 Oct 1;187(7):3499-510. doi: 10.4049/jimmunol.1100424. Epub 2011 Aug 26.

Abstract

During B lymphopoiesis, IL-7 induces survival, proliferation, and differentiation signals that are important during the pro-B to pre-B cell transition. We showed that murine small pre-B stage cells do not signal or proliferate in response to IL-7, yet they maintain IL-7R surface expression. Loss of proliferative responsiveness to IL-7 is mediated by suppressor of cytokine signaling protein 1 (SOCS-1), the expression of which is regulated during B lymphopoiesis, with the highest levels observed in small pre-B cells. SOCS-1 inhibits IL-7 responses in pre-B cell lines and ex vivo B lineage cells. SOCS-1 expression and, thus, responsiveness to IL-7, can be regulated by IL-7 itself, as well as IFN-γ and IL-21. Additionally, the transcriptional repressor Gfi-1b enhances the proliferative responsiveness of B cell lines to IL-7. We demonstrated that these molecules act together to form a SOCS-mediated "rheostat" that controls the level of IL-7R signaling in developing murine B lineage cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Blotting, Western
  • Cell Differentiation
  • Cell Lineage
  • Cell Separation
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Interleukin-7 / immunology*
  • Interleukin-7 / metabolism
  • Lymphopoiesis / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Precursor Cells, B-Lymphoid / cytology
  • Precursor Cells, B-Lymphoid / immunology*
  • Precursor Cells, B-Lymphoid / metabolism
  • Receptors, Interleukin-7 / immunology
  • Receptors, Interleukin-7 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Suppressor of Cytokine Signaling Proteins / immunology*
  • Suppressor of Cytokine Signaling Proteins / metabolism

Substances

  • Interleukin-7
  • Receptors, Interleukin-7
  • Suppressor of Cytokine Signaling Proteins