title: Preferential association of hepatitis C virus with CD19+B cells is mediated by complement system.
abstract: Extrahepatic disease manifestations are common in chronic hepatitis C virus (HCV) infection. The mechanism of HCV-related lymphoproliferative disorders is not fully understood. Recent studies have found that HCV in peripheral blood mononuclear cells from chronically infected patients is mainly associated with cluster of differentiation 19-positive (CD19+) B cells. To further elucidate this preferential association of HCV with B cells, we used in vitro cultured virus and uninfected peripheral blood mononuclear cells from healthy blood donors to investigate the necessary serum components that activate the binding of HCV to B cells. First, we found that the active serum components were present not only in HCV carriers but also in HCV recovered patients and HCV-negative, healthy blood donors and that the serum components were heat-labile. Second, the preferential binding activity of HCV to B cells could be blocked by anti-complement C3 antibodies. In experiments with complement-depleted serum and purified complement proteins, we demonstrated that complement proteins C1, C2, and C3 were required to activate such binding activity. Complement protein C4 was partially involved in this process. Third, using antibodies against cell surface markers, we showed that the binding complex mainly involved CD21 (complement receptor 2), CD19, CD20, and CD81; CD35 (complement receptor 1) was involved but had lower binding activity. Fourth, both anti-CD21 and anti-CD35 antibodies could block the binding of patient-derived HCV to B cells. Fifth, complement also mediated HCV binding to Raji cells, a cultured B-cell line derived from Burkitt's lymphoma.
  
  
  
  In chronic HCV infection, the preferential association of HCV with B cells is mediated by the complement system, mainly through complement receptor 2 (CD21), in conjunction with the CD19 and CD81 complex. (Hepatology 2016;64:1900-1910).
authors.affiliation: Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.
authors.forename: Richard Y
authors.initials: RY
authors.lastname: Wang
authors.affiliation: Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.|Instituto de Investigaciones Hematológicas, Instituto de Medicina Experimental, CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bare
authors.affiliation: Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.
authors.forename: Valeria
authors.initials: V
authors.lastname: De Giorgi
authors.affiliation: Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.|Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuura
authors.affiliation: Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.|Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh.
authors.forename: Kazi Abdus
authors.initials: KA
authors.lastname: Salam
authors.affiliation: Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.
authors.forename: Teresa
authors.initials: T
authors.lastname: Grandinetti
authors.affiliation: Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.
authors.forename: Cathy
authors.initials: C
authors.lastname: Schechterly
authors.affiliation: Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Alter
mesh_terms: D018941:Antigens, CD19; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002478:Cells, Cultured; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D011951:Receptors, Complement / Q000276:immunology*
chemical_list: D018941:Antigens, CD19; D011951:Receptors, Complement