Distinctive Mesenchymal-Parenchymal Cell Pairings Govern B Cell Differentiation in the Bone Marrow

Stem Cell Reports. 2016 Aug 9;7(2):220-35. doi: 10.1016/j.stemcr.2016.06.009. Epub 2016 Jul 21.

Abstract

Bone marrow niches for hematopoietic progenitor cells are not well defined despite their critical role in blood homeostasis. We previously found that cells expressing osteocalcin, a marker of mature osteolineage cells, regulate the production of thymic-seeding T lymphoid progenitors. Here, using a selective cell deletion strategy, we demonstrate that a subset of mesenchymal cells expressing osterix, a marker of bone precursors in the adult, serve to regulate the maturation of early B lymphoid precursors by promoting pro-B to pre-B cell transition through insulin-like growth factor 1 (IGF-1) production. Loss of Osx(+) cells or Osx-specific deletion of IGF-1 led to a failure of B cell maturation and the impaired adaptive immune response. These data highlight the notion that bone marrow is a composite of specialized niches formed by pairings of specific mesenchymal cells with parenchymal stem or lineage committed progenitor cells, thereby providing distinctive functional units to regulate hematopoiesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Cell Differentiation*
  • Insulin-Like Growth Factor I / metabolism
  • Mesoderm / cytology*
  • Mice
  • Sp7 Transcription Factor / metabolism

Substances

  • Sp7 Transcription Factor
  • Sp7 protein, mouse
  • Insulin-Like Growth Factor I