| First Author | Lefebvre JM | Year | 2005 |
| Journal | J Immunol | Volume | 174 |
| Issue | 10 | Pages | 6184-94 |
| PubMed ID | 15879115 | Mgi Jnum | J:99018 |
| Mgi Id | MGI:3580971 | Doi | 10.4049/jimmunol.174.10.6184 |
| Citation | Lefebvre JM, et al. (2005) Enforced expression of Spi-B reverses T lineage commitment and blocks beta-selection. J Immunol 174(10):6184-94 |
| abstractText | The molecular changes that restrict multipotent murine thymocytes to the T cell lineage and render them responsive to Ag receptor signals remain poorly understood. In this study, we report our analysis of the role of the Ets transcription factor, Spi-B, in this process. Spi-B expression is acutely induced coincident with T cell lineage commitment at the CD4(-)CD8(-)CD44(-)CD25(+) (DN3) stage of thymocyte development and is then down-regulated as thymocytes respond to pre-TCR signals and develop beyond the beta-selection checkpoint to the CD4(-)CD8(-)CD44(-)CD25(-) (DN4) stage. We found that dysregulation of Spi-B expression in DN3 thymocytes resulted in a dose-dependent perturbation of thymocyte development. Indeed, DN3 thymocytes expressing approximately five times the endogenous level of Spi-B were arrested at the beta-selection checkpoint, due to impaired induction of Egr proteins, which are important molecular effectors of the beta-selection checkpoint. T lineage-committed DN3 thymocytes expressing even higher levels of Spi-B were diverted to the dendritic cell lineage. Thus, we demonstrate that the prescribed modulation of Spi-B expression is important for T lineage commitment and differentiation beyond the beta-selection checkpoint; and we provide insight into the mechanism underlying perturbation of development when that expression pattern is disrupted. |
