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It is established that the BCR\u2010mediated apoptosis of immature B cells represents an important mechanism for tolerance induction in the pre\u2010immune B cell compartment. We show here that mature germinal center (GC) B cells can re\u2010acquire sensitivity to BCR\u2010induced cell death following CD40 ligation. In contrast, neither virgin nor memory B cells become susceptible to antigen receptor\u2010triggered apoptosis upon CD40 stimulation, suggesting that this phenomenon may play a role in the shaping of the mature B cell repertoire in GC. Our data reveal that the death signal evoked through the BCR does not involve the Fc\u03b3 receptors, does not operate through the Fas\/Fas ligand system, and can be blocked by interleukin\u20104. Finally, we found that the acquisition of sensitivity to the death\u2010promoting effect of anti\u2010Ig antibodies in CD40\u2010stimulated GC B cell cultures correlates with the induction of a centrocytic phenotype. We propose that negative regulatory signals via the BCR may delete somatically mutated centrocytes with self\u2010reactivity.<\/jats:p>","DOI":"10.1002\/eji.1830270210","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T04:33:58Z","timestamp":1172810038000},"page":"405-414","source":"Crossref","is-referenced-by-count":23,"title":["Antigen receptor\u2010induced apoptosis of human germinal center B cells is targeted to a centrocytic subset"],"prefix":"10.1002","volume":"27","author":[{"given":"Gis\u00e8le","family":"Billian","sequence":"first","affiliation":[]},{"given":"Paul","family":"Mondi\u00e8re","sequence":"additional","affiliation":[]},{"given":"Marion","family":"Berard","sequence":"additional","affiliation":[]},{"given":"Chantal","family":"Bella","sequence":"additional","affiliation":[]},{"given":"Thierry","family":"Defrance","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2005,12,5]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60633-1"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/375334a0"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/375331a0"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.6.1635"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/5.10.1259"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.4.1377"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.144.4.882"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/373438a0"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/373441a0"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.1.329"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/7.1.121"},{"key":"e_1_2_1_13_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1146\/annurev.iy.12.040194.001001","volume":"12","author":"MacLennan I. 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