title: B-cell exposure to self-antigen induces IL-10 producing B cells as well as IL-6- and TNF-α-producing B-cell subsets in healthy humans.
abstract: Human B cells are able to secrete IL-10 after stimulation with mitogens, but their ability to produce IL-10 and regulate T-cell responses after stimulation with self-antigens is unclear. We co-cultured thyroglobulin-pulsed B cells from healthy donors with autologous T cells and observed production of IL-10 and TGF-β, in addition to TNF-α and IL-6. Pulsing with foreign antigen, tetanus toxoid (TT), induced a Th1-response with minimal IL-10 production. After thyroglobulin-pulsing, 1.10±0.50% of B cells and 1.00±0.20% of CD4(+) T cells produced IL-10, compared to 0.29±0.19% of B cells (P=0.01) and 0.13±0.15% of CD4(+) T cells (P=0.006) following TT-pulsing. Thyroglobulin-stimulated, IL-10-secreting B cells were enriched within CD5(+) and CD24(high) cells. While thyroglobulin-pulsed B cells induced only modest proliferation of CD4(+) T cells, B cells pulsed with TT induced vigorous proliferation. Thus, B cells mediate self-antigen-specific IL-10, TNF-α and IL-6 production in co-cultures with T cells and contribute actively to these cytokine secretions.
authors.affiliation: Institute for Inflammation Research, Department of Rheumatology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Anina
authors.initials: A
authors.lastname: Langkjær
authors.forename: Birte
authors.initials: B
authors.lastname: Kristensen
authors.forename: Bjarke E
authors.initials: BE
authors.lastname: Hansen
authors.forename: Heidi
authors.initials: H
authors.lastname: Schultz
authors.forename: Laszlo
authors.initials: L
authors.lastname: Hegedüs
authors.forename: Claus H
authors.initials: CH
authors.lastname: Nielsen
mesh_terms: D001324:Autoantigens / Q000276:immunology* / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018920:Coculture Techniques; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology / Q000494:pharmacology; D013954:Thyroglobulin / Q000276:immunology* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D001324:Autoantigens; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D013745:Tetanus Toxoid; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013954:Thyroglobulin