c-Myb Regulates the Survival of CD4+CD8+Double Positive Thymocytes [thesis]

Joan Yuan
The peripheral T cell repertoire is selected during the CD4 + CD8 + double positive (DP) stage of T cell development for optimized pathogen recognition while maintaining selftolerance. Bcl2l1 encodes the survival factor Bcl-xL, which is specifically upregulated in DP thymocytes to prolong the window of time available for Tcrα rearrangements and the generation of a diverse T cell repertoire. However, despite the importance of Bcl2l1 during T cell development, the regulation of its expression
more » ... ins poorly understood. The Myb proto-oncogene encodes an essential transcription factor that plays critical roles during several stages of T cell development including DN to DP thymocyte development, DP thymocyte survival and the development of CD4SP thymocytes. Work in this thesis demonstrates that Myb mRNA expression is specifically upregulated in the small, preselection DP stage during T cell development. Using a conditional deletion model in which deletion at the Myb locus takes place in DP thymocytes, we demonstrate that Myb deficient DP thymocytes undergo premature apoptosis, resulting in a limited Tcrα repertoire biased towards 5' Jα segment usage. Premature apoptosis occurs in an αβ-
doi:10.18130/v30g51 fatcat:bvprxnalprfnvoazvsnriuijuu