Nature Immunology
3, 469 - 476 (2002)
Published online: 22 April 2002; | doi:10.1038/ni791
Regulation of the TCR repertoire by the survival window of CD4+CD8+ thymocytesJian Guo1, Abbas Hawwari1, Hong Li1, Zuoming Sun2, 4, Sanjeev K. Mahanta2, Dan R. Littman2, 3, Michael S. Krangel1
& You-Wen He11
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA. 2
Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York, NY 10016, USA. 3
HHMI, New York University School of Medicine, New York, NY 10016, USA. 4
Present address: Department of Microbiology and Immunology (M/C 790), University of Illinois, 835 S. Wolcott, Chicago, IL 60612, USA.
Correspondence should be addressed to You-Wen He he000004@mc.duke.eduT cell receptor (TCR)  alleles undergo primary and secondary rearrangement in double-positive (DP) thymocytes. By analyzing TCR 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 V to J rearrangements is controlled by DP thymocyte survival. In addition, because Bcl-xL induces a bias towards 3' J 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 J locus and the opportunities for positive selection, thereby regulating the TCR repertoire.
|
