Shimamura M, Ohta S
Laboratory of Molecular Immunology, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Eur J Immunol. 1995 Jun;25(6):1541-6. doi: 10.1002/eji.1830250611.
T cell receptor (TCR) genes are initially activated in hematopoietic stem cells that have been committed to the T cell lineage during ontogeny. We have established cell lines derived from hematopoietic organs which express truncated TCR delta mRNA (1.3 kbp). In this study, cDNA clones of this mRNA were analyzed to characterize TCR delta gene activation in early T cell development. Transcription started from an intron between D delta 2 and J delta 1, 72 bp upstream from J delta 1, and continued to J delta 1 and C delta exons, which were directly spliced to J delta 1. Thus, the truncated mRNA expressed by the cell lines was determined to be a germ-line transcript. The promoter activity of the DNA fragment between D delta 2 and J delta was assessed by its ability to drive the transcription of a reporter gene linked to it in the cell line expressing the TCR delta germ-line transcript. TCR delta germ-line transcription was found not only in these cell lines but also in fetal liver and thymus cells. These findings indicate that the TCR delta germ-line transcription is a naturally occurring event in developing T cells. The significance of germ-line transcription of TCR delta genes is unknown, but it may be an event that follows T-lineage commitment or, at least, may be closely associated with this commitment.
T细胞受体(TCR)基因最初在个体发育过程中已定向为T细胞谱系的造血干细胞中被激活。我们建立了源自造血器官的细胞系,这些细胞系表达截短的TCRδ mRNA(1.3 kbp)。在本研究中,对该mRNA的cDNA克隆进行了分析,以表征早期T细胞发育过程中TCRδ基因的激活情况。转录起始于Dδ2和Jδ1之间的一个内含子,位于Jδ1上游72 bp处,并持续到Jδ1和Cδ外显子,它们直接剪接到Jδ1上。因此,确定细胞系表达的截短mRNA为种系转录本。通过其驱动与表达TCRδ种系转录本的细胞系中与之相连的报告基因转录的能力,评估Dδ2和Jδ之间DNA片段的启动子活性。不仅在这些细胞系中,而且在胎儿肝脏和胸腺细胞中都发现了TCRδ种系转录。这些发现表明,TCRδ种系转录是发育中的T细胞中自然发生的事件。TCRδ基因种系转录的意义尚不清楚,但它可能是T细胞谱系定向之后发生的事件,或者至少可能与该定向密切相关。