Fig 10.

Multiple waves of TCR-α rearrangements during thymocyte development. DNA accessibility in the TCR Jα cluster is regulated such that the first VαJα rearrangements are targeted to the 5′ side of the TCR Jα cluster. If the thymocytes expressing the resulting TCR are not positively selected, Rag1 and Rag2 expression continues, and a second wave of rearrangement involving upstream Vα and downstream Jα segments occurs. In the absence of positive selection of this newly expressed TCR, a third wave of VαJα recombination occurs, and so on. The possibility of thymocytes undergoing several waves of TCR-α rearrangement depends on their life span. In RORγT^−/− mice, thymocyte viability is decreased, resulting in a bias of Jα usage toward the most 5′ elements (first wave). In contrast, the thymocyte life span is increased in BclXL Tg mice, allowing several waves of recombination and the resulting skewing of Jα usage toward the most downstream elements.