TCR-beta repertoire development in the mouse embryo.
We studied the TCR beta-chain repertoire in thymocytes along embryonic development. At day 14 of gestation, complete V-D-J rearrangements of the TCR-beta locus were detected at the messenger RNA level, and a total of 56 different rearrangements were observed in one thymus. At this stage, thymocytes showed preferential usage of TCR-betaV1, TCR-betaV2, and TCR-betaV8 together with TCR-betaJ1S1, -J1S2, and -J2S7 segments. This frequent usage of V and J segments was similar to the usage seen in the adult thymus. Assuming that day 14 thymocytes were not subjected to specificity selection, we conclude that the expression of TCR-betaV and J segments is biased from the beginning of T cell repertoire creation. The first detectable transcripts of rearranged TCR-betas were different among individual fetuses and constituted a random representation of the ones seen at later stages of thymic ontogeny. The diversity of TCR-beta rearrangements increased with time and became indistinguishable from that of the adult by day 16. The first rearranged TCR-alphas were expressed at day 17 and their diversity increased thereafter. We conclude that the diversification of the beta-chain repertoire takes place in 3 days, before the alpha-chain rearrangement begins in transition from CD4/CD8 double negative to double positive cells.
Ema
H
H
Unité 277, INSERM, Département d'Immunologie, Institut Pasteur, Paris, France.
Cumano
A
A
Kourilsky
P
P
D000818:Animals; D004622:Embryo, Mammalian / Q000276:immunology*; D018507:Gene Expression Regulation, Developmental / Q000276:immunology*; D015329:Gene Rearrangement, T-Lymphocyte / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta