{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T05:01:14Z","timestamp":1792904474833,"version":"4.5.0"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1996,3,1]]},"abstract":"<jats:p>During T cell-dependent antibody responses, B cells within germinal centers (GC) alter the affinity of their antigen receptor by introducing somatic mutations into variable region of immunoglobulin (IgV) genes. During this process, GC B cells are destined to die unless positively selected by antigens and CD40-ligand. To understand survival\/death control of germinal center B cell, the expression of four apoptosis-inducing genes, Fas, c-myc, Bax, and P53, together with the survival gene bcl-2, has been analyzed herein among purified tonsillar naive, GC, and memory B cells. IgD+CD38- naive B cells were separated into CD23- (mature B cell [Bm]1) subset and CD23+ (Bm2), IgD-CD38+ GC B cells were separated into subsets of CD77+ centroblasts (Bm3) and CD77- centrocytes (Bm4), whereas IgD-CD38- cells represented the Bm5 memory B cell subset. Sequence analysis of IgV region genes indicated that somatic hypermutation was triggered in the Bm3 centroblast subset. Here we show that bcl-2 is only detectable with naive (Bm1 and 2) and memory B cell (Bm5) subsets, whereas all four apoptosis-inducing genes were most significantly expressed within GC B cells. Fas was equally expressed in Bm3 centroblasts and Bm4 centrocytes, whereas Bax was most significantly expressed in Bm4 centrocytes. c-myc, a positive regulator of cell cycle, was most significantly expressed in proliferating Bm3 centroblasts, whereas P53, a negative regulator of cell cycle, was most signficantly expressed in nonproliferating Bm4 centrocytes. The present results indicate that the survival\/death of GC B cells are regulated by the up- and downregulation of multiple genes, among which the expression of c-myc and P53 in the absence of bcl-2 may prime the proliferating Bm3 centroblasts and nonproliferating Bm4 centrocytes to apoptosis.<\/jats:p>","DOI":"10.1084\/jem.183.3.971","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"971-977","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":167,"title":["Human germinal center B cells express the apoptosis-inducing genes Fas, c-myc, P53, and Bax but not the survival gene bcl-2."],"prefix":"10.1084","volume":"183","author":[{"given":"H","family":"Martinez-Valdez","sequence":"first","affiliation":[{"name":"Schering-Plough, Laboratory for Immunological Research, Dardilly, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Guret","sequence":"additional","affiliation":[{"name":"Schering-Plough, Laboratory for Immunological Research, Dardilly, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"de Bouteiller","sequence":"additional","affiliation":[{"name":"Schering-Plough, Laboratory for Immunological Research, Dardilly, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Fugier","sequence":"additional","affiliation":[{"name":"Schering-Plough, Laboratory for Immunological Research, Dardilly, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Banchereau","sequence":"additional","affiliation":[{"name":"Schering-Plough, Laboratory for Immunological Research, Dardilly, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y J","family":"Liu","sequence":"additional","affiliation":[{"name":"Schering-Plough, Laboratory for Immunological Research, Dardilly, France."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1996,3,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/183\/3\/971\/1678572\/971.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/183\/3\/971\/1678572\/971.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T07:14:31Z","timestamp":1690269271000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/183\/3\/971\/47881\/Human-germinal-center-B-cells-express-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,3,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1996,3,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.183.3.971","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,3,1]]}}}