Cell circuits between B cell progenitors and IL-7+ mesenchymal progenitor cells control B cell development

J Exp Med. 2018 Oct 1;215(10):2586-2599. doi: 10.1084/jem.20180778. Epub 2018 Aug 29.

Abstract

B cell progenitors require paracrine signals such as interleukin-7 (IL-7) provided by bone marrow stromal cells for proliferation and survival. Yet, how B cells regulate access to these signals in vivo remains unclear. Here we show that proB and IL-7+ cells form a cell circuit wired by IL-7R signaling, which controls CXCR4 and focal adhesion kinase (FAK) expression and restricts proB cell movement due to increased adhesion to IL-7+CXCL12Hi cells. PreBCR signaling breaks this circuit by switching the preB cell behavior into a fast-moving and lower-adhesion state via increased CXCR4 and reduced FAK/α4β1 expression. This behavioral change reduces preB cell exposure to IL-7, thereby attenuating IL-7R signaling in vivo. Remarkably, IL-7 production is downregulated by signals provided by preB cells with unrepaired double-stranded DNA breaks and by preB acute lymphoblastic leukemic cells. Combined, these studies revealed that distinct cell circuits control the quality and homeostasis of B cell progenitors.

Publication types

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

MeSH terms

  • Animals
  • Chemokine CXCL12 / genetics
  • Interleukin-7 / genetics
  • Interleukin-7 / immunology*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / immunology*
  • Mice
  • Mice, Knockout
  • Precursor Cells, B-Lymphoid / cytology
  • Precursor Cells, B-Lymphoid / immunology*
  • Receptors, Interleukin-7 / genetics
  • Receptors, Interleukin-7 / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*

Substances

  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Interleukin-7
  • Receptors, Interleukin-7