Candéias S, Hardy R R, Li Y S, Staerz U D
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Eur J Immunol. 1994 Dec;24(12):3073-81. doi: 10.1002/eji.1830241224.
Rearrangement of the T cell antigen receptor (TCR) beta chain genes is highly regulated in both a developmental and a tissue-specific manner. T cell precursors originate from the yolk sac or fetal liver during gestation and from the bone marrow during adulthood. They initiate the recombination of TCR genes primarily during differentiation in the thymus. It has previously been suggested that transcription of immunoglobulin genes in germ-line configuration is linked to recombination events within these loci. Here, we examine whether germ-line transcription of TCR variable genes coincides with their rearrangement or whether it marks even earlier stages of T lymphocyte development. During gestation, we found V beta 8.2 germ-line transcripts in the fetal liver and the fetal thymus, but not in the yolk sac. This transcription precedes V beta 8.2 to D beta J beta rearrangement. In adult animals, we found these transcripts in the thymus, the spleen, the liver and the bone marrow. However, in the liver, this transcription is dependent on the presence of mature lymphocytes. This transcription does not happen in non-lymphoid cells. In the B lymphocyte lineage, V beta 8.2 germ-line transcripts are detected only in the earliest stages of differentiation (pre-pro- and pro-B cells), but not in pre-B cells and mature B lymphocytes. Altogether, our results show that transcription of the unrearranged V beta 8.2 gene is an early event of lymphocyte development, taking place in lymphocyte precursors, long before V beta 8.2 rearrangement.
T细胞抗原受体（TCR）β链基因的重排以发育和组织特异性方式受到高度调控。T细胞前体在妊娠期起源于卵黄囊或胎儿肝脏，成年期起源于骨髓。它们主要在胸腺分化过程中启动TCR基因的重组。此前有人提出，种系构型的免疫球蛋白基因转录与这些基因座内的重组事件相关。在这里，我们研究TCR可变基因的种系转录是否与其重排同时发生，或者它是否标志着T淋巴细胞发育的更早阶段。在妊娠期，我们在胎儿肝脏和胎儿胸腺中发现了Vβ8.2种系转录本，但在卵黄囊中未发现。这种转录先于Vβ8.2至DβJβ重排。在成年动物中，我们在胸腺、脾脏、肝脏和骨髓中发现了这些转录本。然而，在肝脏中，这种转录依赖于成熟淋巴细胞的存在。非淋巴细胞中不会发生这种转录。在B淋巴细胞谱系中，仅在分化的最早阶段（前前B细胞和前B细胞）检测到Vβ8.2种系转录本，而在pre-B细胞和成熟B淋巴细胞中未检测到。总之，我们的结果表明，未重排的Vβ8.2基因的转录是淋巴细胞发育的早期事件，发生在淋巴细胞前体中，远早于Vβ8.2重排。
