| First Author | Yuan J | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 6 | Pages | 2793-804 |
| PubMed ID | 20142358 | Mgi Jnum | J:160124 |
| Mgi Id | MGI:4453441 | Doi | 10.4049/jimmunol.0902846 |
| Citation | Yuan J, et al. (2010) c-Myb promotes the survival of CD4+CD8+ double-positive thymocytes through upregulation of Bcl-xL. J Immunol 184(6):2793-804 |
| abstractText | Mechanisms that regulate the lifespan of CD4(+)CD8(+) double-positive (DP) thymocytes help shape the peripheral T cell repertoire. However, the molecular mechanisms controlling DP thymocyte survival remain poorly understood. The Myb proto-oncogene encodes a transcription factor required during multiple stages of T cell development. We demonstrate that Myb mRNA expression is upregulated as thymocytes differentiate from the double-negative into the metabolically quiescent, small, preselection DP stage during T cell development. Using a conditional deletion mouse model, we demonstrate that Myb-deficient DP thymocytes undergo premature apoptosis, resulting in a limited Tcralpha repertoire biased toward 5' Jalpha segment usage. Premature apoptosis occurs specifically in the small preselection DP compartment in an alphabetaTCR-independent manner and is a consequence of decreased Bcl-xL expression. Forced Bcl-xL expression is able to rescue survival, and reintroduction of c-Myb restores both Bcl-xL expression and the small preselection DP compartment. We further demonstrate that c-Myb promotes transcription at the Bcl2l1 locus via a genetic pathway that is independent of the expression of T cell-specific factor-1 or RORgammat, two transcription factors that induce Bcl-xL expression in T cell development. Thus, Bcl-xL is a novel mediator of c-Myb activity during normal T cell development. |
