{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:45:08Z","timestamp":1790203508392,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T00:00:00Z","timestamp":1411603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Chronic hepatitis C virus (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>) infection is characterized by persistent B\u2010cell activation, with enhanced differentiation and reduced proliferative ability. To assess the possible role of <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> in altering B\u2010cell subset distribution, we examined <jats:italic>ex vivo<\/jats:italic> frequencies and B\u2010cell inhibitory receptor expression in 37 chronic <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010infected patients and 25 healthy donors (<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>). In addition, we determined whether short\u2010term exposure to culture\u2010derived <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>cc) resulted in B\u2010cell subset skewing and\/or activation. There was a statistically significant increase in the frequencies of immature transitional, activated memory and tissue\u2010like memory (<jats:styled-content style=\"fixed-case\">TLM<\/jats:styled-content>) B cells in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010infected patients compared with <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>. We also found that the frequency of memory B cells correlated with serum <jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content> levels. The proportion of B cells expressing the marker of exhaustion Fc receptor\u2010like 4 (Fc<jats:styled-content style=\"fixed-case\">RL<\/jats:styled-content>4) was generally low even though significantly higher in the patients' memory B\u2010cell compartment compared with <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>, and a positive correlation was found between the frequencies of the patients' <jats:styled-content style=\"fixed-case\">TLM<\/jats:styled-content> Fc<jats:styled-content style=\"fixed-case\">RL<\/jats:styled-content>4+ B cells and serum alanine aminotransferase and histological activity index at liver biopsy. Exposure to cell\u2010free <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>cc <jats:italic>in vitro<\/jats:italic> did not result in B\u2010cell skewing but induced significant activation of na\u00efve, <jats:styled-content style=\"fixed-case\">TLM<\/jats:styled-content> and resting memory B cells in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010infected patients but not in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>, in whom cell\u2010associated virus was an absolute requirement for activation of memory B cells. These findings provide corroborative evidence in favour of significant B\u2010cell subset skewing in chronic <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection and in addition show that expression of exhaustion markers in selected B\u2010cell subsets does not impair virus\u2010induced B\u2010cell activation.<\/jats:p>","DOI":"10.1111\/jvh.12336","type":"journal-article","created":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T09:30:46Z","timestamp":1411637446000},"page":"391-398","source":"Crossref","is-referenced-by-count":38,"title":["Skewed B cells in chronic hepatitis C virus infection maintain their ability to respond to virus\u2010induced activation"],"prefix":"10.1111","volume":"22","author":[{"given":"B.","family":"Oliviero","sequence":"first","affiliation":[{"name":"Research Laboratories Department of Infectious Diseases Fondazione IRCCS Policlinico San Matteo Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Mantovani","sequence":"additional","affiliation":[{"name":"Research Laboratories Department of Infectious Diseases Fondazione IRCCS Policlinico San Matteo Pavia Italy"},{"name":"Department of Internal Medicine and Therapeutics University of Pavia Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ludovisi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Therapeutics University of Pavia Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Varchetta","sequence":"additional","affiliation":[{"name":"Research Laboratories Department of Infectious Diseases Fondazione IRCCS Policlinico San Matteo Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Mele","sequence":"additional","affiliation":[{"name":"Research Laboratories Department of Infectious Diseases Fondazione IRCCS Policlinico San Matteo Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Paolucci","sequence":"additional","affiliation":[{"name":"Molecular Virology Unit Microbiology and Virology Service Fondazione IRCCS Policlinico San Matteo Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Baldanti","sequence":"additional","affiliation":[{"name":"Molecular Virology Unit Microbiology and Virology Service Fondazione IRCCS Policlinico San Matteo Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. U.","family":"Mondelli","sequence":"additional","affiliation":[{"name":"Research Laboratories Department of Infectious Diseases Fondazione IRCCS Policlinico San Matteo Pavia Italy"},{"name":"Department of Internal Medicine and Therapeutics University of Pavia Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,25]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-200303000-00006"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-09-3679"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509402102"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.10.016"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25821"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0068308"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000879"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.3.1506"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.181347898"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25723"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45685"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510310136"},{"key":"e_1_2_5_14_1","first-page":"827254","article-title":"B lymphocytes: development, tolerance, and their role in autoimmunity\u2010focus on systemic lupus erythematosus","volume":"2013","author":"Tob\u00f3n GJ","year":"2013","journal-title":"Autoimmune Dis"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12067"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/829584"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02155-13"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1006\/clim.2001.5195"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.8.3923-3934.2006"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072683"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.182.2.890"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050879"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-243071"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-012-9677-0"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201142313"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103139"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-353102"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.10.6532"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-07-101717"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.4.1023"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.13.3745"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.12336","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.12336","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.12336","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T19:16:55Z","timestamp":1696187815000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.12336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,25]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,4]]}},"alternative-id":["10.1111\/jvh.12336"],"URL":"https:\/\/doi.org\/10.1111\/jvh.12336","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,25]]}}}