{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:51:49Z","timestamp":1791312709677,"version":"4.3.1"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":167,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Major Science and Technology Special Project of China","award":["2012ZX10002-003"],"award-info":[{"award-number":["2012ZX10002-003"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DK39588"],"award-info":[{"award-number":["DK39588"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81470836"],"award-info":[{"award-number":["81470836"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>\n                    The serological hallmark of primary biliary cirrhosis (PBC) is the presence of high titer and specific antimitochondrial antibodies (AMAs). Although there is no global immune defect in patients with PBC, there is widespread dysregulated B\u2010cell function, including increased sera levels of immunoglobulin M and enhanced B\u2010cell responses to cytosine\u2010phosphate\u2010guanine stimulation. The mechanisms involved in this B\u2010cell dysfunction have remained unknown. To address this issue, we focused on identifying the frequencies of B\u2010cell subsets in patients with PBC and the mechanisms that lead to B\u2010cell dysregulation, including the relationships with chemokine (C\u2010X\u2010C motif) receptor 5 (CXCR5)\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Herein, we report that elevations of both serum and intrahepatic interleukin\u201021 (IL\u201021) were found in patients with PBC and, in particular, promoted B\u2010cell proliferation, signal transducer and activator of transcription 3 phosphorylation and AMA production\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    . More important, upon stimulation with recombinant E2 subunit of pyruvate dehydrogenase complex, CXCR5\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in PBC produced higher levels of IL\u201021 than healthy controls. Additionally, sorted CXCR5\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells increased production of AMAs by autologous CD19\n                    <jats:sup>+<\/jats:sup>\n                    B cells. Indeed, elevated expression of intrahepatic chemokine (C\u2010X\u2010C motif) ligand 13 (CXCL13), a key chemokine of CXCR5\n                    <jats:sup>+<\/jats:sup>\n                    cells, was uniquely found within the portal tracts in PBC, accompanied by infiltrates of CD4\n                    <jats:sup>+<\/jats:sup>\n                    , CXCR5\n                    <jats:sup>+<\/jats:sup>\n                    , CD19\n                    <jats:sup>+<\/jats:sup>\n                    , and CD38\n                    <jats:sup>+<\/jats:sup>\n                    cells.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : CXCL13 promotes aggregation of CD19\n                    <jats:sup>+<\/jats:sup>\n                    B cells and CXCR5\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, which directs the aberrant AMA response by IL\u201021. These data have implications for potential immunotherapy and also reflect the unique lymphoid biology in liver of PBC. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2015;61:1998\u20102007)\n                  <\/jats:p>","DOI":"10.1002\/hep.27725","type":"journal-article","created":{"date-parts":[[2015,1,27]],"date-time":"2015-01-27T18:08:22Z","timestamp":1422382102000},"page":"1998-2007","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":54,"title":["Chemokine (C\u2010X\u2010C motif) ligand 13 promotes intrahepatic chemokine (C\u2010X\u2010C motif) receptor 5+ lymphocyte homing and aberrant B\u2010cell immune responses in primary biliary cirrhosis"],"prefix":"10.1097","volume":"61","author":[{"given":"Yongyin","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Organ Failure Research,Guangdong Provincial Key Laboratory of Viral Hepatitis Research,Department of Infectious Diseases and Hepatology Unit,Nanfang Hospital, Southern Medical University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weibin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research,Guangdong Provincial Key Laboratory of Viral Hepatitis Research,Department of Infectious Diseases and Hepatology Unit,Nanfang Hospital, Southern Medical University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libo","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research,Guangdong Provincial Key Laboratory of Viral Hepatitis Research,Department of Infectious Diseases and Hepatology Unit,Nanfang Hospital, Southern Medical University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanqiu","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research,Guangdong Provincial Key Laboratory of Viral Hepatitis Research,Department of Infectious Diseases and Hepatology Unit,Nanfang Hospital, Southern Medical University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research,Guangdong Provincial Key Laboratory of Viral Hepatitis Research,Department of Infectious Diseases and Hepatology Unit,Nanfang Hospital, Southern Medical University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research,Guangdong Provincial Key Laboratory of Viral Hepatitis Research,Department of Infectious Diseases and Hepatology Unit,Nanfang Hospital, Southern Medical University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youfu","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research,Guangdong Provincial Key Laboratory of Viral Hepatitis Research,Department of Infectious Diseases and Hepatology Unit,Nanfang Hospital, Southern Medical University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research,Guangdong Provincial Key Laboratory of Viral Hepatitis Research,Department of Infectious Diseases and Hepatology Unit,Nanfang Hospital, Southern Medical University,Guangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongquan","family":"Shi","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Xijing Hospital of Digestive Diseases,Fourth Military Medical University,Xi'an,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Renji Hospital, School of Medicine, Shanghai Jiao Tong University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R.","family":"Mackay","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology,Monash University,Clayton,Victoria,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Eric","family":"Gershwin","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology,University of California,Davis,CA,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Han","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Xijing Hospital of Digestive Diseases,Fourth Military Medical University,Xi'an,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlin","family":"Hou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research,Guangdong Provincial Key Laboratory of Viral Hepatitis Research,Department of Infectious Diseases and Hepatology Unit,Nanfang Hospital, Southern Medical University,Guangzhou,China"},{"name":"Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,Zhejiang 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