title: The V(H) repertoire and clonal diversification of B cells in inflammatory myopathies.
abstract: The contribution of antigen-driven B-cell adaptive immune responses within the inflamed muscle of inflammatory myopathies (IMs) is largely unknown. In this study, we investigated the immunoglobulin V(H) gene repertoire, somatic hypermutation, clonal diversification, and selection of infiltrating B cells in muscle biopsies from IM patients (dermatomyositis and polymyositis), to determine whether B cells and/or plasma cells contribute to the associated pathologies of these diseases. The data reveal that Ig V(H) gene repertoires of muscle-infiltrating B cells deviate from the normal V(H) gene repertoire in individual patients, and differ between different types of IMs. Analysis of somatic mutations revealed clonal diversification of muscle-infiltrating B cells and evidence for a chronic B-cell response within the inflamed muscle. We conclude that muscle-infiltrating B cells undergo selection, somatic hypermutation and clonal diversification in situ during antigen-driven immune responses in patients with IMs, providing insight into the contribution of B cells to the pathological mechanisms of these disorders.
authors.affiliation: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: Donna
authors.initials: D
authors.lastname: McIntyre
authors.forename: Neta S
authors.initials: NS
authors.lastname: Zuckerman
authors.forename: Max
authors.initials: M
authors.lastname: Field
authors.forename: Ramit
authors.initials: R
authors.lastname: Mehr
authors.forename: David I
authors.initials: DI
authors.lastname: Stott
mesh_terms: D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D009132:Muscles / Q000276:immunology / Q000378:metabolism; D009154:Mutation / Q000235:genetics / Q000276:immunology; D009220:Myositis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000941:Antigens; D007143:Immunoglobulin Heavy Chains
keywords: B cell; Clonal diversification; Myositis; Somatic hypermutation; V-gene repertoire