부산대학교 도서관

T cell receptor (TCR) a alleles undergo primary and secondary rearrangement in double-positive (DP) thymocytes. By analyzing TCRa rearrangement in orphan nuclear receptor ROR?-deficient mice, in which the DP lifespan is shorter, and in Bcl-xL-transgenic mice, in which the DP lifespan is extended, we show that the progression of secondary Va to Ja rearrangements is controlled by DP thymocyte survival. In addition, because Bcl-xL induces a bias towards 3' Ja usage in peripheral T cells, we conclude that the programmed cell death of DP thymocytes is not simply a consequence of failed positive selection. Rather, it limits the progression of rearrangement along the Ja locus and the opportunities for positive selection, thereby regulating the TCRa repertoire. [ABSTRACT FROM AUTHOR]