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DP stage\u2013specific deletion of the E3 ligase Cul3, or of Bcl6, induced the derepression of the Bcl6 target genes Batf (basic leucine zipper transcription factor, ATF-like) and Bcl6, in part through epigenetic modifications of CD4+ single-positive thymocytes. Although they maintained an apparently normal phenotype after emigration, they expressed increased amounts of Batf and Bcl6 at basal state and produced explosive and prolonged Tfh responses upon subsequent antigen encounter. Ablation of Cul3 in mature CD4+ splenocytes also resulted in dramatically exaggerated Tfh responses. Thus, although previous studies have emphasized the essential role of Bcl6 in inducing Tfh responses, our findings reveal that Bcl6\u2013Cul3 complexes also provide essential negative feedback regulation during both thymocyte development and T cell activation to restrain excessive Tfh responses.<\/jats:p>","DOI":"10.1084\/jem.20132267","type":"journal-article","created":{"date-parts":[[2014,5,27]],"date-time":"2014-05-27T02:50:26Z","timestamp":1401159026000},"page":"1137-1151","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["A negative feedback loop mediated by the Bcl6\u2013cullin 3 complex limits Tfh cell differentiation"],"prefix":"10.1084","volume":"211","author":[{"given":"Rebecca","family":"Mathew","sequence":"first","affiliation":[{"name":"Committee on Immunology 1 , 2 , 3 , and 4"},{"name":"Department of Pathology 1 , 2 , 3 , and 4"},{"name":"Howard Hughes Medical Institute 1 , 2 , 3 , and 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