| First Author | Patton DT | Year | 2014 |
| Journal | J Immunol | Volume | 193 |
| Issue | 7 | Pages | 3446-55 |
| PubMed ID | 25143441 | Mgi Jnum | J:267164 |
| Mgi Id | MGI:6259053 | Doi | 10.4049/jimmunol.1302925 |
| Citation | Patton DT, et al. (2014) The survival and differentiation of pro-B and pre-B cells in the bone marrow is dependent on IL-7Ralpha Tyr449. J Immunol 193(7):3446-55 |
| abstractText | IL-7 is critical for murine T and B cell development and survival and plays a significant role in lymphoblastic leukemia in both humans and mice. We evaluated the role of the IL-7Ralpha Tyr(449) cytoplasmic SH2-binding motif in IL-7-mediated B cell development using a knock-in mouse with a Tyr to Phe mutation (IL-7Ralpha(449F/449F) mouse). IL-7Ralpha(449F/449F) and IL-7Ralpha(-/-) mice showed no defect in the number of pre-pro-B cells, although IL-7Ralpha(449F/449F) mice had decreased Ebf1 in pre-pro-B cells and impairment in B cell-committed CLPs. We identified that IL-7Ralpha Tyr(449) was critical for both pro-B and pre-B stages of development in the bone marrow. IL-7Ralpha(449F/449F) and IL-7Ralpha(-/-) mice had comparable precursor B cell defects, indicating that signaling from the IL-7Ralpha required this motif. Although the defect in IL-7Ralpha(449F/449F) pro-B cells was associated with loss of STAT5 activation and diminished expression of Mcl1, this was not rescued by overexpression of Bcl-2. IL-7Ralpha(449F/449F) and IL-7Ralpha(-/-) pre-B cells also showed defective cyto-Igmu and CD25 expression, associated with reduced levels of Rag1, Rag2, and Irf4. Pre-B cells from IL-7Ralpha(449F/449F) mice also failed to proliferate, perhaps as a result of the failure to rearrange Igmu. Our data suggest that IL-7Ralpha Tyr(449) was essential for IL-7Ralpha signaling in bone marrow B cell development and survival. |
