Regulation of N-region diversity in antigen receptors through thymocyte differentiation and thymus ontogeny

The random addition of "N nucleotides" by terminal deoxynucleotidyltransferase (TdT) is an important component of the diversity of T-cell receptor genes. We have investigated the expression of TdT during thymocyte differentiation and thymus ontogeny. TdT gene transcripts are confined to immature thymocytes of the cortex, being down-regulated concomitantly with recombination-activating gene transcripts after positive selection of mature medullary T cells. According to in situ hybridization, TdT RNA is absent from the neonatal thymus, but it appears 3 to 5 days after birth, just before the appearance of significant N-region diversity in T-cell receptor junctional sequences but clearly after the thymus attains competence at clonal deletion.