Regulation of the TCRalpha repertoire by the survival window of CD4(+)CD8(+) thymocytes.
T cell receptor (TCR) alpha alleles undergo primary and secondary rearrangement in double-positive (DP) thymocytes. By analyzing TCRalpha rearrangement in orphan nuclear receptor RORgamma-deficient mice, in which the DP lifespan is shorter, and in Bcl-x(L)-transgenic mice, in which the DP lifespan is extended, we show that the progression of secondary V(alpha) to J(alpha) rearrangements is controlled by DP thymocyte survival. In addition, because Bcl-x(L) induces a bias towards 3' J(alpha) 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(alpha) locus and the opportunities for positive selection, thereby regulating the TCRalpha repertoire.
Guo
Jian
J
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Hawwari
Abbas
A
Li
Hong
H
Sun
Zuoming
Z
Mahanta
Sanjeev K
SK
Littman
Dan R
DR
Krangel
Michael S
MS
He
You-Wen
YW
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002843:Chromatin / Q000276:immunology; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D005434:Flow Cytometry; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000276:immunology*; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D013047:Specific Pathogen-Free Organisms; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D002843:Chromatin; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D019253:Proto-Oncogene Proteins c-bcl-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse; D051020:bcl-X Protein; D004247:DNA