Up-regulation of telomerase in human B lymphocytes occurs independently ofcellular proliferation and with expression of the telomerase catalytic subunit

Telomerase activity is up-regulated 1000-fold higher in human tonsil germin al center B cells compared to resting naive or memory B cells, and telomera se expression can be reactivated in vitro resting B cells. To understand th e mechanism(s) of telomerase regulation, quiescent B cell from peripheral b lood or tonsil were activated with different combinations of various stimul i. Cross-linking surface (s)IgD or sIgM of B cells induced marked up-regula tion of telomerase enzymatic activity in the absence of cellular proliferat ion. Low level crosslinkage of surface molecules by soluble anti-IgM did no t up-regulate the telomerase activity. However, the inability of soluble an ti-IgM to up-regulate the telomerase activity was corrected by additional s ignals from soluble anti-CD40 antibody engagement or IL-4/IL-10. Activation of B cell proliferation with Epstein-Barr virus failed to up-regulate telo merase, further suggesting that up-regulation of telomerase is an event ind ependent of B cell proliferation. Telomerase induction occurred in the late G1 phase of the cell cycle and did not require entry into S phase. Up-regu lation of telomerase enzymatic activity correlated primarily with the induc tion of expression of the hTERT gene, the catalytic subunit to telomerase, suggesting that control of telomerase regulation resides at the level of th e catalytic subunit of this holoenzyme.