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

Chris Fistonich, Sandra Zehentmeier, Jeffrey J. Bednarski, Runfeng Miao, Hilde Schjerven, Barry P. Sleckman, João P. Pereira

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


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.

Original languageEnglish
Pages (from-to)2586-2599
Number of pages14
JournalJournal of Experimental Medicine
Issue number10
StatePublished - Oct 1 2018


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