title: Intrahepatic B-cell follicles of chronically hepatitis C virus-infected individuals lack signs of an ectopic germinal center reaction.
abstract: Chronic infection with hepatitis C virus (HCV) often affects the B-cell compartment, leading to the occurrence of autoimmunity and B-cell lymphoproliferation, in particular mixed cryoglobulinemia and B-cell lymphomas. HCV presumably causes these lymphoproliferations by chronic antigenic stimulation and/or direct mutagenic effects on B cells. It has been speculated that the interaction of HCV with B cells and the expansion of antigen-triggered B cells happens in germinal center-like structures in the livers of HCV carriers. We studied rearranged immunoglobulin V(H) genes from seven B-cell follicles microdissected from the livers of three unselected chronic HCV patients. The follicles consisted of polyclonal naive and memory B-cell populations with only rare indication of minor clonal expansions and no evidence for active somatic hypermutation. Frequent detection of V(H) rearrangements using the VH1-69 gene segment nevertheless indicated that at least a fraction of the B cells is HCV-specific and/or autoreactive. Thus, the typical intrahepatic B-cell follicles in chronic HCV carriers do not function as ectopic germinal centers for clonal expansion and affinity maturation of B cells. Hence, autoreactive and HCV-specific B-cell clones might either develop in secondary lymphoid organs or in intrahepatic follicles only under particular, yet undefined, circumstances.
authors.affiliation: Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany.
authors.forename: Felicia A
authors.initials: FA
authors.lastname: Tucci
authors.forename: Ruth
authors.initials: R
authors.lastname: Broering
authors.forename: Melanie
authors.initials: M
authors.lastname: Lutterbeck
authors.forename: Joerg F
authors.initials: JF
authors.lastname: Schlaak
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D005260:Female; D018858:Germinal Center / Q000276:immunology* / Q000473:pathology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics / Q000276:immunology*
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region
keywords: B-cell clonal expansion; Germinal centers; HCV; IgVH genes; Somatic hypermutation