| First Author | Fahl SP | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 10 | Pages | 3450-3463 |
| PubMed ID | 29654210 | Mgi Jnum | J:261461 |
| Mgi Id | MGI:6155478 | Doi | 10.4049/jimmunol.1302303 |
| Citation | Fahl SP, et al. (2018) c-Myb Coordinates Survival and the Expression of Genes That Are Critical for the Pre-BCR Checkpoint. J Immunol 200(10):3450-3463 |
| abstractText | The c-Myb transcription factor is required for adult hematopoiesis, yet little is known about c-Myb function during lineage-specific differentiation due to the embryonic lethality of Myb-null mutations. We previously used tissue-specific inactivation of the murine Myb locus to demonstrate that c-Myb is required for differentiation to the pro-B cell stage, survival during the pro-B cell stage, and the pro-B to pre-B cell transition during B lymphopoiesis. However, few downstream mediators of c-Myb-regulated function have been identified. We demonstrate that c-Myb regulates the intrinsic survival of CD19(+) pro-B cells in the absence of IL-7 by repressing expression of the proapoptotic proteins Bmf and Bim and that levels of Bmf and Bim mRNA are further repressed by IL-7 signaling in pro-B cells. c-Myb regulates two crucial components of the IL-7 signaling pathway: the IL-7Ralpha-chain and the negative regulator SOCS3 in CD19(+) pro-B cells. Bypassing IL-7R signaling through constitutive activation of Stat5b largely rescues survival of c-Myb-deficient pro-B cells, whereas constitutively active Akt is much less effective. However, rescue of pro-B cell survival is not sufficient to rescue proliferation of pro-B cells or the pro-B to small pre-B cell transition, and we further demonstrate that c-Myb-deficient large pre-B cells are hypoproliferative. Analysis of genes crucial for the pre-BCR checkpoint demonstrates that, in addition to IL-7Ralpha, the genes encoding lambda5, cyclin D3, and CXCR4 are downregulated in the absence of c-Myb, and lambda5 is a direct c-Myb target. Thus, c-Myb coordinates survival with the expression of genes that are required during the pre-BCR checkpoint. |
