TELOMERASE IS UP-REGULATED IN HUMAN GERMINAL CENTER B-CELLS IN-VIVO AND CAN BE RE-EXPRESSED IN MEMORY B-CELLS ACTIVATED IN-VITRO

The extensive proliferation that B lymphocytes undergo in germinal cen ters could compromise generation of long term B cell memory if there o ccurs shortening of the telomeres of germinal center B cells with cell division. Telomere length, which is thought to act as a ''mitotic clo ck'' for somatic cells that dictates cellular senescence, can be prese rved by the enzyme telomerase. Human tonsil germinal center B cells co nsistently expressed 100- to 1000-fold higher levels of telomerase act ivity than naive or memory B cells, which had no or very low detectabl e activity, as analyzed by the telomere repeat amplification protocol assay. In vitro stimulation of human memory B cells through surface Ig or CD40 was capable of up-regulating telomerase. The findings suggest that longevity of B cell memory is maintained, despite multiple cell divisions in the generation of a memory B cell, by upregulation of tel omerase in germinal center and activated memory B cells.