| First Author | Fistonich C | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 10 | Pages | 2586-2599 |
| PubMed ID | 30158115 | Mgi Jnum | J:270221 |
| Mgi Id | MGI:6203421 | Doi | 10.1084/jem.20180778 |
| Citation | Fistonich C, et al. (2018) Cell circuits between B cell progenitors and IL-7(+) mesenchymal progenitor cells control B cell development. J Exp Med 215(10):2586-2599 |
| abstractText | 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(+)CXCL12(Hi) 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/alpha4beta1 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. |
