title: Clonal Characteristics of Circulating B Lymphocyte Repertoire in Primary Biliary Cholangitis.
abstract: Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by elevated serum anti-mitochondrial Ab and lymphocyte-mediated bile duct damage. This study was designed to reveal the clonal characteristics of B lymphocyte repertoire in patients with PBC to facilitate better understanding of its pathogenesis and better management of these patients. Using high-throughput sequencing of Ig genes, we analyzed the repertoire of circulating B lymphocytes in 43 patients with PBC, and 34 age- and gender-matched healthy controls. Compared with healthy controls, PBC patients showed 1) a gain of 14 new clones and a loss of 8 clones; 2) a significant clonal expansion and increased relative IgM abundance, which corresponded with the elevated serum IgM level; 3) a significant reduction of clonal diversity and somatic hypermutations in class-switched sequences, which suggested a general immunocompromised status; 4) the reduction of clonal diversity and enhancement of clonal expansion were more obvious at the cirrhotic stage; and 5) treatment with ursodeoxycholic acid could increase the clonal diversity and reduce clonal expansion of the IgM repertoire, with no obvious effect on the somatic hypermutation level. Our data suggest that PBC is a complex autoimmune disease process with evidence of B lymphocyte clonal gains and losses, Ag-dependent ogligoclonal expansion, and a generally compromised immune reserve. This new insight into the pathogenesis of PBC opens up the prospect of studying disease-relevant B cells to better diagnose and treat this devastating disease.
authors.affiliation: Central Laboratory of Infection and Immunity, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China; Department of Clinical Laboratory, FuXing Hospital, Capital Medical University, Beijing 100038, China;
authors.forename: Yan-Guo
authors.initials: YG
authors.lastname: Tan
authors.affiliation: Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin 300308, China; BGI-Shenzhen, Shenzhen 518083, China;
authors.forename: Yu-Qi
authors.identifier: 0000-0002-4014-3271
authors.initials: YQ
authors.lastname: Wang
authors.affiliation: Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin 300308, China; BGI-Shenzhen, Shenzhen 518083, China;
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin 300308, China; BGI-Shenzhen, Shenzhen 518083, China;
authors.forename: Ying-Xin
authors.initials: YX
authors.lastname: Han
authors.affiliation: Department of Liver Disease Immunology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China;
authors.forename: Chun-Yang
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Central Laboratory of Infection and Immunity, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China;
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, FuXing Hospital, Capital Medical University, Beijing 100038, China;
authors.forename: Zhuo-Min
authors.initials: ZM
authors.lastname: Li
authors.affiliation: Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin 300308, China; BGI-Shenzhen, Shenzhen 518083, China;
authors.forename: Xiao-Lei
authors.identifier: 0000-0001-5015-4460
authors.initials: XL
authors.lastname: Wu
authors.affiliation: Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin 300308, China; BGI-Shenzhen, Shenzhen 518083, China;
authors.forename: Xiao-Feng
authors.identifier: 0000-0002-7051-7254
authors.initials: XF
authors.lastname: Wang
authors.affiliation: Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin 300308, China; BGI-Shenzhen, Shenzhen 518083, China;
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin 300308, China; BGI-Shenzhen, Shenzhen 518083, China;
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Zhu
authors.affiliation: Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin 300308, China; BGI-Shenzhen, Shenzhen 518083, China;
authors.forename: Shi-da
authors.identifier: 0000-0002-8352-2175
authors.initials: SD
authors.lastname: Zhu
authors.affiliation: Tianjin Translational Genomics Center, BGI-Tianjin, Tianjin 300308, China; BGI-Shenzhen, Shenzhen 518083, China;
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Li
authors.affiliation: Department of Surgery, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China; zu-hua.gao@mcgill.ca yhp503@126.com liningbjyah@vip.sina.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Central Laboratory of Infection and Immunity, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China; zu-hua.gao@mcgill.ca yhp503@126.com liningbjyah@vip.sina.com.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Yan
authors.affiliation: Department of Pathology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China; and Department of Pathology, McGill University, Montreal, Quebec H3A 2B4, Canada zu-hua.gao@mcgill.ca yhp503@126.com liningbjyah@vip.sina.com.
authors.forename: Zu-Hua
authors.identifier: 0000-0001-7232-0933
authors.initials: ZH
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D002761:Cholangitis / Q000276:immunology* / Q000503:physiopathology; D002999:Clone Cells; D005260:Female; D014644:Genetic Variation / Q000187:drug effects; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D007075:Immunoglobulin M; D014580:Ursodeoxycholic Acid