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

Academic Article

Abstract

  • © 2018 Fistonich et al. 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.
  • Digital Object Identifier (doi)

    Author List

  • Fistonich C; Zehentmeier S; Bednarski JJ; Miao R; Schjerven H; Sleckman BP; Pereira JP
  • Start Page

  • 2586
  • End Page

  • 2599
  • Volume

  • 215