CpG inhibits pro-B cell expansion through a cathepsin B-dependent mechanism

J Immunol. 2010 May 15;184(10):5678-85. doi: 10.4049/jimmunol.0903854. Epub 2010 Apr 16.

Abstract

TLR9 is expressed in cells of the innate immune system, as well as in B lymphocytes and their progenitors. We investigated the effect of the TLR9 ligand CpG DNA on the proliferation of pro-B cells. CpG DNA inhibits the proliferation of pro-B, but not pre-B, cells by inducing caspase-independent cell death through a pathway that requires the expression of cathepsin B. This pathway is operative in Rag-deficient mice carrying an SP6 transgene, in which B lymphopoiesis is compromised, to reduce the size of the B lymphocyte precursor compartments in the bone marrow. Thus, TLR9 signals can regulate B lymphopoiesis in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / cytology*
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • Caspases / physiology
  • Cathepsin B / deficiency
  • Cathepsin B / genetics
  • Cathepsin B / physiology*
  • Cell Death / immunology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cell Line
  • Cell Proliferation
  • Cells, Cultured
  • CpG Islands / physiology*
  • Homeostasis / immunology
  • Interleukin-7 / physiology
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Signal Transduction / immunology
  • Stem Cells / cytology*
  • Stem Cells / immunology*
  • Stem Cells / metabolism
  • Toll-Like Receptor 9 / deficiency
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / physiology

Substances

  • Interleukin-7
  • Ligands
  • Tlr9 protein, mouse
  • Toll-Like Receptor 9
  • Caspases
  • Cathepsin B
  • Ctsb protein, mouse