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Here, we show that liver tissue collected at the time of liver transplantation in two patients with HBV-associated ALF is characterized by an overwhelming B cell response apparently centered in the liver with massive accumulation of plasma cells secreting IgG and IgM, accompanied by complement deposition. We demonstrate that the molecular target of these antibodies is the hepatitis B core antigen (HBcAg); that these anti-bodies display a restricted variable heavy chain (V\n                    <jats:sub>H<\/jats:sub>\n                    ) repertoire and lack somatic mutations; and that these two unrelated individuals with ALF use an identical predominant V\n                    <jats:sub>H<\/jats:sub>\n                    gene with unmutated variable domain (\n                    <jats:italic>IGHV1-3<\/jats:italic>\n                    ) for both IgG and IgM anti-HBc antibodies, indicating that HBcAg is the target of a germline human V\n                    <jats:sub>H<\/jats:sub>\n                    gene. These data suggest that humoral immunity may exert a primary role in the pathogenesis of HBV-associated ALF.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1003854107","type":"journal-article","created":{"date-parts":[[2010,4,26]],"date-time":"2010-04-26T21:49:06Z","timestamp":1272318546000},"page":"8766-8771","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":115,"title":["B cell gene signature with massive intrahepatic production of antibodies to hepatitis B core antigen in hepatitis B virus\u2013associated acute liver failure"],"prefix":"10.1073","volume":"107","author":[{"given":"Patrizia","family":"Farci","sequence":"first","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Diaz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Technologies, University of Cagliari, 09123 Cagliari, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaochun","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sugantha","family":"Govindarajan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Rancho Los Amigos Hospital, Downey, CA 90242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Tice","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liane","family":"Agulto","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Pittaluga","sequence":"additional","affiliation":[{"name":"Hematopathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denali","family":"Boon","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claro","family":"Yu","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald E.","family":"Engle","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Simon","sequence":"additional","affiliation":[{"name":"Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Purcell","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Zamboni","sequence":"additional","affiliation":[{"name":"Liver Transplantation Center, Brotzu Hospital, 09134 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,4,26]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1056\/NEJM199312163292508","article-title":"Acute liver failure","volume":"329","author":"Lee WM","year":"1993","unstructured":"WM Lee, Acute liver failure. 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