title: Antigen-presenting human B cells are expanded in inflammatory conditions.
abstract: Traditionally, B cells have been best known for their role as producers of antibodies. However, in recent years, a growing body of evidence has accumulated showing that B cells fulfill a range of other immunologic functions. One of the functions that has attracted increasing attention is the capacity of B cells to induce antigen-specific activation of T cells through presentation of antigens. However, the analysis of this B cell function has been hampered by the lack of a phenotypically well-defined antigen-presenting B cell subset. Here, we report the identification of a human antigen-presenting B cell subset with strong immunostimulatory properties. This B cell subset is characterized by low expression of CD21 and high expression of the activation marker CD86 and exhibits strong T cell-stimulatory activity, as demonstrated by means of an autologous mixed-lymphocyte reaction. Phenotypically, CD21lowCD86posimmunostimulatory B cells (BAPC) represented CD27+class-switched IgMnegIgDnegB lymphocytes and displayed a higher expression of cell surface receptors, which mediate the migration from peripheral blood to sites of inflammation. Flow cytometric analysis of peripheral blood obtained from individuals with inflammatory conditions revealed that the BAPCsubset was expanded following vaccination and in patients with rheumatoid arthritis. Taken together, our work shows that BAPCrepresents a strongly immunostimulatory B cell subset, which could be a promising target for immunotherapeutic intervention in inflammatory diseases.
authors.affiliation: Cologne Interventional Immunology, University Hospital of Cologne, Cologne, Germany; alexander.shimabukuro-vornhagen@uk-koeln.de.|Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Shimabukuro-Vornhagen
authors.affiliation: Cologne Interventional Immunology, University Hospital of Cologne, Cologne, Germany.|Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: María
authors.initials: M
authors.lastname: García-Márquez
authors.affiliation: Cologne Interventional Immunology, University Hospital of Cologne, Cologne, Germany.|Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Rieke N
authors.initials: RN
authors.lastname: Fischer
authors.affiliation: Cologne Interventional Immunology, University Hospital of Cologne, Cologne, Germany.|Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Iltgen-Breburda
authors.affiliation: Cologne Interventional Immunology, University Hospital of Cologne, Cologne, Germany.|Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Fiedler
authors.affiliation: Cologne Interventional Immunology, University Hospital of Cologne, Cologne, Germany.|Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wennhold
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, Cologne, Germany; and.
authors.forename: Gunter
authors.initials: G
authors.lastname: Rappl
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, Cologne, Germany; and.
authors.forename: Hinrich
authors.initials: H
authors.lastname: Abken
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Clara
authors.initials: C
authors.lastname: Lehmann
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Herling
authors.affiliation: Medical Clinic III, Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Wolf
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rubbert-Roth
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.affiliation: Cologne Interventional Immunology, University Hospital of Cologne, Cologne, Germany.|Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Theurich
authors.affiliation: Cologne Interventional Immunology, University Hospital of Cologne, Cologne, Germany.|Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: von Bergwelt-Baildon
mesh_terms: D000328:Adult; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D051940:B7-2 Antigen / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology* / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000378:metabolism; D015398:Signal Transduction; D014611:Vaccination
chemical_list: D051940:B7-2 Antigen; D011947:Receptors, Antigen, B-Cell; D019707:Receptors, Chemokine; D017464:Receptors, Complement 3d; D023201:CD40 Ligand
keywords: APC; B cell subsets; inflammation; rheumatoid arthritis