title: Increased IgA production by B-cells in COPD via lung epithelial interleukin-6 and TACI pathways.
abstract: Despite their relevance to mucosal defense, production of IgA and the function of lung B-cells remain unknown in chronic obstructive pulmonary disease (COPD). We assessed IgA synthesis in the lungs of COPD (n=28) and control (n=21) patients, and regulation of B-cells co-cultured with in vitro-reconstituted airway epithelium. In COPD lung tissue, synthesis of IgA1 was increased, which led to its accumulation in subepithelial areas. In vitro, the COPD bronchial epithelium imprinted normal human B-cells for increased production of IgA (mainly IgA1) and maturation into CD38(+) plasma cells. These effects were associated with upregulation of TACI (transmembrane activator and CAML interactor) and were observed under resting conditions, while being partly inhibited upon stimulation with cigarette smoke extract. Interleukin (IL)-6 and BAFF (B-cell activating factor)/APRIL (a proliferation-inducing ligand) were upregulated in the COPD epithelium and lung tissue, respectively; the IgA-promoting effect of the COPD bronchial epithelium was inhibited by targeting IL-6 and, to a lower extent, by blocking TACI. These data show that in COPD, the bronchial epithelium imprints B-cells with signals promoting maturation into IgA-producing plasma cells through the action of two epithelial/B-cell axes, namely the IL-6/IL-6 receptor and BAFF-APRIL/TACI pathways, while cigarette smoke partly counteracts this IgA-promoting effect.
authors.affiliation: Université Catholique de Louvain (UCL), Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Pneumologie, ORL et Dermatologie, Brussels, Belgium Cliniques universitaires St-Luc, Service de Pneumologie, Brussels, Belgium Institute for Walloon Excellence in Lifesciences and Biotechnology (WELBIO), Brussels, Belgium.
authors.forename: Maha Zohra
authors.initials: MZ
authors.lastname: Ladjemi
authors.affiliation: Université Catholique de Louvain (UCL), Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Pneumologie, ORL et Dermatologie, Brussels, Belgium Cliniques universitaires St-Luc, Service de Pneumologie, Brussels, Belgium Institute for Walloon Excellence in Lifesciences and Biotechnology (WELBIO), Brussels, Belgium.
authors.forename: Marylène
authors.initials: M
authors.lastname: Lecocq
authors.affiliation: CHU de Mont-Godinne, Service d'anatomopathologie, Yvoir, Belgium.
authors.forename: Birgit
authors.initials: B
authors.lastname: Weynand
authors.affiliation: MRC/Asthma UK Centre in Allergic Mechanisms of Asthma, Randall Division of Cell and Molecular Biophysics, King's College London, London, UK.
authors.forename: Holly
authors.initials: H
authors.lastname: Bowen
authors.affiliation: MRC/Asthma UK Centre in Allergic Mechanisms of Asthma, Randall Division of Cell and Molecular Biophysics, King's College London, London, UK.
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Gould
authors.affiliation: UCL, C. de Duve Institute of Cellular Pathology, Brussels, Belgium Ludwig Institute for Cancer Research, Brussels, Belgium.
authors.forename: Jacques
authors.initials: J
authors.lastname: Van Snick
authors.affiliation: Université Catholique de Louvain (UCL), Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Pneumologie, ORL et Dermatologie, Brussels, Belgium Cliniques universitaires St-Luc, Service de Pneumologie, Brussels, Belgium Institute for Walloon Excellence in Lifesciences and Biotechnology (WELBIO), Brussels, Belgium.
authors.forename: Bruno
authors.initials: B
authors.lastname: Detry
authors.affiliation: Université Catholique de Louvain (UCL), Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Pneumologie, ORL et Dermatologie, Brussels, Belgium Cliniques universitaires St-Luc, Service de Pneumologie, Brussels, Belgium Institute for Walloon Excellence in Lifesciences and Biotechnology (WELBIO), Brussels, Belgium charles.pilette@uclouvain.be.
authors.forename: Charles
authors.initials: C
authors.lastname: Pilette
mesh_terms: D015415:Biomarkers; D016022:Case-Control Studies; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000473:pathology*; D012313:RNA / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D018709:Statistics, Nonparametric; D053303:Transmembrane Activator and CAML Interactor Protein / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D007070:Immunoglobulin A; D015850:Interleukin-6; C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D012313:RNA