title: Innate Response Activator (IRA) B Cells Reside in Human Tonsils and Internalize Bacteria In Vitro.
abstract: Innate response activator (IRA) B cells have been described in mice as a subset of B-1a B cells that produce granulocyte/macrophage colony-stimulating factor (GM-CSF) and have been found in the spleen upon activation. In humans, identification, tissue localization and functionality of these lymphocytes are poorly understood. We hypothesized that IRA B cells could reside in human palatine tonsils, which are a first line of defense from infection of the upper respiratory tract. In the present work, we used flow cytometry and confocal microscopy to identify and characterize human IRA (hIRA) B cells in tonsils. We show that CD19⁺CD20⁺GM-CSF⁺ B cells are present in the tonsils of all the subjects studied at a frequency ranging between ~0.2% and ~0.4% of the conventional CD19⁺CD20⁺GM-CSF⁻ B cells. These cells reside within the B cell follicles, are mostly IgM⁺IgD⁺, express CD5 and show phagocytic activity. Our results support a role for hIRA B cells in the effector immune response to infections in tonsils.
authors.affiliation: Novartis Vaccines and Diagnostics (a GSK company), Research Center, Via Fiorentina 1, Siena, Italy.
authors.forename: Nico
authors.initials: N
authors.lastname: Chiappini
authors.affiliation: Novartis Vaccines and Diagnostics (a GSK company), Research Center, Via Fiorentina 1, Siena, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Cantisani
authors.affiliation: Novartis Vaccines and Diagnostics (a GSK company), Research Center, Via Fiorentina 1, Siena, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pancotto
authors.affiliation: Novartis Vaccines and Diagnostics (a GSK company), Research Center, Via Fiorentina 1, Siena, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ruggiero
authors.affiliation: Novartis Vaccines and Diagnostics (a GSK company), Research Center, Via Fiorentina 1, Siena, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Rosa
authors.affiliation: Novartis Vaccines and Diagnostics (a GSK company), Research Center, Via Fiorentina 1, Siena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Manetti
authors.affiliation: Otorhinolaryngology Department, University Hospital Le Scotte, Strada delle Scotte 14, Siena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Romano
authors.affiliation: Department of Medical Biotechnologies, Infectious Unit, University Hospital Le Scotte, Strada delle Scotte 14, Siena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Montagnani
authors.affiliation: Novartis Vaccines and Diagnostics (a GSK company), Research Center, Via Fiorentina 1, Siena, Italy.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bertholet
authors.affiliation: Novartis Vaccines and Diagnostics (a GSK company), Research Center, Via Fiorentina 1, Siena, Italy.
authors.forename: Flora
authors.initials: F
authors.lastname: Castellino
authors.affiliation: Novartis Vaccines and Diagnostics (a GSK company), Research Center, Via Fiorentina 1, Siena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
mesh_terms: D000293:Adolescent; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D018951:Antigens, CD20 / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D018956:CD5 Antigens / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis; D013211:Staphylococcus aureus / Q000472:pathogenicity
chemical_list: D018941:Antigens, CD19; D018951:Antigens, CD20; D018956:CD5 Antigens; D016178:Granulocyte-Macrophage Colony-Stimulating Factor