The ends of linear chromosomes are composed of telomeres which contribute to the maintenance of chromosomal integrity. Telomere shortening occurs with cell division and may provide a mechanism for limiting the replicative potential of normal human somatic cells. Telomerase, a ribonucleoprotein enzyme, is capable of synthesizing telomeric repeats on chromosomal termini, potentially extending the capacity for cell division. The present study analyzes the regulation of telomerase activity in murine T and B cells stimulated in vitro and in vivo with receptor-specific and polyclonal stimuli. Splenic T and B cells have low/undetectable telomerase activity, but substantial telomerase activity is induced by in vitro stimulation with a variety of T cell- and B cell-specific stimuli. Further analysis of T cell activation by antigen-specific stimulation in vitro demonstrates that optimal induction of telomerase requires both TcR and CD28-B7 costimulatory signals. Preliminary analysis of antigen receptor-specific T cell and B cell activation in vivo demonstrates that telomerase activity is induced in vivo as well as in vitro and that induction of telomerase activity in vivo correlates with the appearance of receptor-activated cycling cells.
|Original language||English (US)|
|State||Published - Mar 20 1998|