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 centers could compromise generation of long term B cell memory if there occurs shortening of the telomeres of germinal center B cells with cell division. Telomere length, which is thought to act as a "mitotic clock" for somatic cells that dictates cellular senescence, can be preserved by the enzyme telomerase. Human tonsil germinal center B cells consistently expressed 100- to 1000-fold higher levels of telomerase activity than naive or memory B cells, which had no or very low detectable 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 up-regulation of telomerase in germinal center and activated memory B cells.
Hu
B T
BT
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Lee
S C
SC
Marin
E
E
Ryan
D H
DH
Insel
R A
RA
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D018858:Germinal Center / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D007072:Immunoglobulin D / Q000032:analysis; D007156:Immunologic Memory; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000032:analysis; D014066:Palatine Tonsil; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D007072:Immunoglobulin D; D008562:Membrane Glycoproteins; D019098:Telomerase; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1