Developmental T cell receptor gene rearrangements: relatedness of the alpha/beta and gamma/delta T cell precursor

Abstract

To examine the relationships between T cell populations at various stages of development, T cell receptor (TcR) gene rearrangements were compared between the four murine populations of (a) early thymocytes, (b) early splenocytes, (c) adult thymocytes and (d) adult splenocytes. TcR alpha gene rearrangements were shown to progress from 5' to 3' regions of the J alpha locus and from 3' to 5' regions of the V alpha locus during the development of T cells in both the thymus and spleen. Thus, the gene rearrangement potentials of proximal genes varied with age, yielding a biased repertoire in the young vs. adult animal. As evidence that gamma/delta and alpha/beta gene rearrangements appeared concomitantly in individual precursors, it was found that: (a) multiple adult thymocytes bore alpha gene rearrangements on one chromosome and delta gene rearrangements on the homologous chromosome, and (b) V gamma 3-J gamma 1 rearrangements, prominent joins in the early gamma/delta T cell population, were also prominent in the early alpha/beta T cell subset. These data illustrate the non-random nature of the developmental TcR gene rearrangement and suggest that alpha/beta and gamma/delta T cell populations derive from related, if not identical, T cell precursor populations.