Nonrandom use of Jα gene segments: Influence of Vα and Jα gene location

TCR genes (α, β, γ, and δ) undergo rearrangement during development in the thymus. The repertoire of αβ and γδ 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, α chain transcripts from different stages of ontogeny were examined to determine the influence of V and J gene location on the thymic repertoire. Jα gene segments were not used equally by Vα genes. The frequency of Jα use, and thus the α 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 Jα region preferentially use the most 5' Jα gene segments. In contrast, a Vα gene that is distal to the Jα region was rarely joined to these same 5' Jα 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 VαJα rearranged gene would be replaced by the joining of a flanking Vα gene to a flanking Jα gene segment. Finally, the evidence suggests that there may be differences in the extent of secondary rearrangements between fetal and adult animals.