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In contrast to previous observations, in which telomere shortening and concomitant loss of replicative potential occur in the process of somatic cell differentiation and cell division, it was found that germinal center (GC) B cells, a compartment characterized by extensive clonal expansion and selection, had significantly longer telomeric restriction fragments than those of precursor naive B cells. Furthermore, it was found that telomerase, a telomere-synthesizing enzyme, is expressed at high levels in GC B cells (at least 128-fold higher than those of naive and memory B cells), correlating with the long telomeres in this subset of B cells. Finally, both naive and memory B cells were capable of up-regulating telomerase activity\n                    <jats:italic>in vitro<\/jats:italic>\n                    in response to activation signals through the B cell antigen receptor in the presence of CD40 engagement and\/or interleukin 4. These observations suggest that a novel process of telomere lengthening, possibly mediated by telomerase, functions in actively dividing GC B lymphocytes and may play a critical role in humoral immune response by maintaining the replicative potential of GC and descendant memory B cells.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.20.10827","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:44Z","timestamp":1027679504000},"page":"10827-10832","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":223,"title":["Telomere lengthening and telomerase activation during human B cell\u2009differentiation"],"prefix":"10.1073","volume":"94","author":[{"given":"Nan-ping","family":"Weng","sequence":"first","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute, and National Institute on Aging, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Granger","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute, and National Institute on Aging, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Hodes","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute, and National Institute on Aging, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1997,9,30]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/302575a0"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/381751a0"},{"key":"e_1_3_2_3_2","first-page":"55","volume":"4","author":"Liu Y J","year":"1996","unstructured":"Y J Liu, J Banchereau The Immunologist 4, 55\u201366 (1996).","journal-title":"The Immunologist"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(95)80010-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/smim.1996.0022"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.1.329"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(93)90145-B"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60536-2"},{"key":"e_1_3_2_9_2","first-page":"123","volume-title":"Cellular Aging and Cell Death","author":"Greider C W","year":"1996","unstructured":"C W Greider, C B Harley Cellular Aging and Cell Death, eds N J Holbrook, G R Martin, R A Lockshin (Wiley\u2013Liss, New York), pp. 123\u2013138 (1996)."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/350569a0"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5242.1601"},{"key":"e_1_3_2_12_2","first-page":"69","volume-title":"Telomeres","author":"Fang G","year":"1995","unstructured":"G Fang, T R Cech Telomeres, eds E H Blackburn, C W Greider (Cold Spring Harbor Lab. 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