The level of N‐region diversity in T cell receptors is not pre‐ordained in the stem cell

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Abstract
The αβ Tcell repertoires of adults and neonates are distinctly different. For example. Tcell receptors (TcR) from adult animals have substantial N‐nucleotide addition at their V‐D‐J junctions while those from neonatal animals do not. This dichotomy reflects a rather abrupt change in expression of the terminal deoxynucleotidyl transferase (TdT) gene in thymocytes on day 4 after birth. We have asked whether this change is due to the differentiation of successive waves of stem cells harboring different potentials for TdT expression, a scenario like the one proposed to explain developmental regulation of γδ Tcell repertoires. Reconstitution of adult severe combined immunodeficiency mice with either fetal liver or adult bone marrow precursors gave rise to T cells with substantial N‐region diversity in their TcR, even at the earliest points of reconstitution. It is most likely, then, that the abrupt change in TdT gene expression in day 4 thymocytes is due to an environmentally induced switch‐on.