Ema H, Cumano A, Kourilsky P
Unité 277, INSERM, Département d'Immunologie, Institut Pasteur, Paris, France.
J Immunol. 1997 Nov 1;159(9):4227-32.
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.
我们研究了胚胎发育过程中胸腺细胞的TCRβ链库。在妊娠第14天，在信使RNA水平检测到TCR-β基因座的完整V-D-J重排，在一个胸腺中总共观察到56种不同的重排。在此阶段，胸腺细胞优先使用TCR-βV1、TCR-βV2和TCR-βV8以及TCR-βJ1S1、-J1S2和-J2S7区段。V和J区段的这种频繁使用与成年胸腺中的使用情况相似。假设第14天的胸腺细胞未经过特异性选择，我们得出结论，TCR-βV和J区段的表达从T细胞库创建之初就存在偏差。重排的TCR-β的首次可检测转录本在个体胎儿之间有所不同，并且构成了胸腺个体发育后期所见转录本的随机表现。TCR-β重排的多样性随时间增加，并在第16天时与成年个体的多样性变得难以区分。首次重排的TCR-α在第17天表达，此后其多样性增加。我们得出结论，β链库的多样化在3天内发生，即在从CD4/CD8双阴性细胞向双阳性细胞转变的过程中α链重排开始之前。
