T-CELL RECEPTOR V-BETA-8.2 GENE GERM-LINE TRANSCRIPTION - AN EARLY EVENT OF LYMPHOCYTE DIFFERENTIATION

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.