Nonrandom use of J alpha gene segments. Influence of V alpha and J alpha gene location.

Abstract

TCR genes (alpha, beta, gamma, and delta) undergo rearrangement during development in the thymus. The repertoire of alpha beta and gamma delta cells is shaped first by genetic processes that control rearrangement and expression and then by intercellular processes that "select" cells expressing only particular receptors. In this report, alpha chain transcripts from different stages of ontogeny were examined to determine the influence of V and J gene location on the thymic repertoire. J alpha gene segments were not used equally by V alpha genes. The frequency of J alpha use, and thus the alpha chain repertoire, was influenced by at least three factors: the location of the V gene, the location of the J gene, and the age of the animal. V genes that are proximal to the J alpha region preferentially use the most 5' J alpha gene segments. In contrast, a V alpha gene that is distal to the J alpha region was rarely joined to these same 5' J alpha gene segments in thymocytes from adult animals. We suggest that the data are most easily explained by the frequent occurrence of secondary rearrangements in which a V alpha J alpha rearranged gene would be replaced by the joining of a flanking V alpha gene to a flanking J alpha gene segment. Finally, the evidence suggests that there may be differences in the extent of secondary rearrangements between fetal and adult animals.