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Here, we characterize the transgenic line pK\u03ba with this split tolerance phenotype and assess the effects of B cell competition and the survival cytokine BAFF (B cell activating factor belonging to the TNF family) on peripheral tolerance. In pK\u03ba mice the surviving peritoneal and splenic \u03ba<jats:sup>+<\/jats:sup>B cells were largely lost in mice carrying one copy of the human C\u03ba exon in place of the mouse version, a maneuver that generates additional antigen non\u2010reactive competitor B cells in this model. Furthermore, overexpression of BAFF suppressed \u03ba\u2010macroself antigen\u2010induced deletion and promoted production of both IgM,\u03ba and IgA,\u03ba antibodies in mice with normal Ig\u03ba alleles but not in mice carrying one copy of the human C\u03ba allele. These findings suggest that BAFF overexpression has minimal effects on the survival of autoreactive B cells in a polyclonal immune system and that B cell:B cell competition plays a potent role in suppressing the survival of B\u20101 and splenic B cells with excessive autoreactivity.<\/jats:p>","DOI":"10.1002\/eji.200535581","type":"journal-article","created":{"date-parts":[[2006,3,2]],"date-time":"2006-03-02T09:19:01Z","timestamp":1141291141000},"page":"985-996","source":"Crossref","is-referenced-by-count":13,"title":["Effect of cell:cell competition and BAFF expression on peripheral B cell tolerance and B\u20101 cell survival in transgenic mice expressing a low level of Ig\u03ba\u2010reactive macroself antigen"],"prefix":"10.1002","volume":"36","author":[{"given":"Djemel","family":"A\u00eft\u2010Azzouzene","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda\u2004L.","family":"Gavin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Skog","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao","family":"Duong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Nemazee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,3,29]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/334676a0"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/349331a0"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/354308a0"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/4.2.163"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/371389a0"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.2.425"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.1.125"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80285-X"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1159\/000066853"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.15.5687"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/352532a0"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/11.5.765"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5462.2501"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.05.010"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20022144"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00079-2"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.1.129"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00183-2"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061964"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00481-X"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.11.1697"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5425.260"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.7.3370"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.7.953"},{"key":"e_1_2_7_25_2","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/S0022-3565(24)38768-3","article-title":"Pharmacokinetics and immunological effects of exogenously administered recombinant human B lymphocyte stimulator (BLyS) in mice.","volume":"296","author":"Parry T. 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