| First Author | Klein F | Year | 2019 |
| Journal | J Exp Med | Volume | 216 |
| Issue | 3 | Pages | 638-655 |
| PubMed ID | 30765463 | Mgi Jnum | J:275319 |
| Mgi Id | MGI:6305987 | Doi | 10.1084/jem.20181444 |
| Citation | Klein F, et al. (2019) The transcription factor Duxbl mediates elimination of pre-T cells that fail beta-selection. J Exp Med 216(3):638-655 |
| abstractText | T cell development is critically dependent on successful rearrangement of antigen-receptor chains. At the beta-selection checkpoint, only cells with a functional rearrangement continue in development. However, how nonselected T cells proceed in their dead-end fate is not clear. We identified low CD27 expression to mark pre-T cells that have failed to rearrange their beta-chain. Expression profiling and single-cell transcriptome clustering identified a developmental trajectory through beta-selection and revealed specific expression of the transcription factor Duxbl at a stage of high recombination activity before beta-selection. Conditional transgenic expression of Duxbl resulted in a developmental block at the DN3-to-DN4 transition due to reduced proliferation and enhanced apoptosis, whereas RNA silencing of Duxbl led to a decrease in apoptosis. Transcriptome analysis linked Duxbl to elevated expression of the apoptosis-inducing Oas/RNaseL pathway. RNaseL deficiency or sustained Bcl2 expression led to a partial rescue of cells in Duxbl transgenic mice. These findings identify Duxbl as a regulator of beta-selection by inducing apoptosis in cells with a nonfunctional rearrangement. |
