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

TCR genes (α, β, γ, and δ) undergo rearrangement uring development in the thymus. The repertoire f αβ and γδ cells is shaped first by genetic processes hat control rearrangement and expression and hen by intercellular processes that "select" cells xpressing only particular receptors. In this report, chain transcripts from different stages of ontogny were examined to determine the influence of V nd J gene location on the thymic repertoire. Jα ene segments were not used equally by Vα genes, The frequency of Jα use, and thus the α chain reprtoire, was influenced by at least three factors: the ocation of the V gene, the location of the J gene, nd the age of the animal. V genes that are proximal o the Ja region preferentially use the most 5′ Jα ene segments. In contrast, a Vα gene that is distal o the Ja region was rarely joined to these same 5′ α gene segments in thymocytes from adult animals. We suggest that the data are most easily exlained by the frequent occurrence of secondary earrangements in which a VαJα rearranged gene would be replaced by the joining of a flanking Vα ene to a flanking Jα gene segment. Finally, the evidence suggests that there may be differences in he extent of secondary rearrangements between etal and adult animals.