Vβ Gene Repertoire in the Aging Mouse: A Developmental Perspective

Abstract

To define age-associated alterations in the immune system at the molecular level, we have analyzed TCR Vβ gene expression patterns at the fetal, neonatal, adult, and advanced ages of mice. In contrast to Vγ and V_H genes, Vβ genes rearranged without any preference related to their chromosomal organization. Endogenous superantigen-mediated clonal deletions were registered for the first time at the neonatal stage, presumably reflecting the late developmental appearance of these molecules. Such deletions, once established, were maintained throughout life with little, if any, leakage in this process. Furthermore, bone marrow transplantation and other studies indicated that an involuted thymus maintained its capacity to perform both its functions, i.e. positive and negative selection. Although overall Vβ repertoires showed remarkable stability with advanced age, modifications in expression levels for some Vβ, particularly those associated with the CD8 subset and presumably reflecting antigenic stimulation, were recorded. Mice with lupus and early-life thymic involution were fully capable of deleting endogenous superantigen-reactive Vβ clones, and even lupus mice with a genetic defect in the apoptosis-promoting Fas gene were normal in this regard. The results indicate that, aside from some anticipated clonal expansions induced by antigenic stimulation, age-associated alterations in immune functions are not caused by any profound changes in the overall TCR repertoire.

Key Words:

• aging
• T cell receptors
• Vβ genes
• superantigens
• apoptosis