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Antibody affinity is increased through germinal center (GC) affinity maturation, which relies on BCR somatic hypermutation (SHM) followed by antigen-based selection. GC B cell proliferation is essentially involved in these processes; it provides enough templates for SHM and also serves as a critical mechanism of positive selection. In this study, we show that expression of epigenetic regulator ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) was markedly up-regulated by c-Myc\u2013AP4 in GC B cells, and it was required for GC response. Uhrf1 regulates cell proliferation\u2013associated genes including cdkn1a, slfn1, and slfn2 by DNA methylation, and its deficiency inhibited the GC B cell cycle at G1-S phase. Subsequently, GC B cell SHM and affinity maturation were impaired, and Uhrf1 GC B knockout mice were unable to control chronic virus infection. Collectively, our data suggest that Uhrf1 regulates GC B cell proliferation and affinity maturation, and its expression in GC B cells is required for virus clearance.<\/jats:p>","DOI":"10.1084\/jem.20171815","type":"journal-article","created":{"date-parts":[[2018,4,4]],"date-time":"2018-04-04T11:25:11Z","timestamp":1522841111000},"page":"1437-1448","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["Uhrf1 regulates germinal center B cell expansion and affinity maturation to control viral infection"],"prefix":"10.1084","volume":"215","author":[{"given":"Chao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Immunology, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7974-8430","authenticated-orcid":true,"given":"Sulan","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Immunology, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immunology, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehui","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Immunology, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2263-128X","authenticated-orcid":true,"given":"Jun","family":"Qin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Stem Cell Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences\/Shanghai Jiao Tong University School of Medicine, Shanghai, China 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology, Department of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, China 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Huo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0679-9768","authenticated-orcid":true,"given":"Xiaoming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2018,4,4]]},"reference":[{"key":"2023072604105837100_bib1","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.immuni.2007.07.009","article-title":"Germinal-center organization and cellular dynamics","volume":"27","author":"Allen","year":"2007","journal-title":"Immunity."},{"key":"2023072604105837100_bib2","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1084\/jem.20151682","article-title":"Ubiquitin-mediated fluctuations in MHC class II facilitate efficient germinal center B cell responses","volume":"213","author":"Bannard","year":"2016","journal-title":"J. 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