title: Regulatory B cells in CVID patients fail to suppress multifunctional IFN-γ+ TNF-α+ CD4+ T cells differentiation.
abstract: Common variable immunodeficiency (CVID) refers to primary hypogammaglobulinemia with unknown pathogenesis. Although there is evidence for intrinsic B cell defects in some CVID patient groups, various abnormalities in cytokine production by T cells in CVID patients are frequently observed. Here, we demonstrate a relationship in the production of pro-inflammatory Th1 cytokines and regulatory B cells producing IL-10 between CVID patients and healthy controls. We describe CD19(+)CD24(hi)CD38(hi)IL-10(+) regulatory B cells generated after T cell stimulation of human peripheral blood lymphocytes ex vivo are able to suppress IFN-γ(+)TNF-α(+) producing CD4(+) T cells. This process is impaired in CVID patients, who present with both low numbers of CD19(+)CD24(hi)CD38(hi)IL-10(+) B cells and increased numbers of IFN-γ(+)TNF-α(+)CD4(+) T cells. Disruption of the regulatory B cell response to T cell stimulation explains the excessive T cell activation regarded as an immunoregulatory abnormality that is a frequent finding in CVID patients.
authors.affiliation: Department of Clinical Immunology and Allergy, St. Anne's Faculty Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic. Electronic address: marcela.vlkova@fnusa.cz.
authors.forename: Marcela
authors.initials: M
authors.lastname: Vlkova
authors.affiliation: Department of Clinical Immunology and Allergy, St. Anne's Faculty Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Olga
authors.initials: O
authors.lastname: Ticha
authors.affiliation: Department of Clinical Immunology and Allergy, St. Anne's Faculty Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Nechvatalova
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, 2nd Medical Faculty, Charles University Prague, University Hospital Motol, Prague, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Kalina
authors.affiliation: Department of Clinical Immunology and Allergy, St. Anne's Faculty Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Litzman
authors.affiliation: Centre for Rheumatology Research, Division of Medicine, University College London, 5 University Street, London WC1E 6JF, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mauri
authors.affiliation: Centre for Rheumatology Research, Division of Medicine, University College London, 5 University Street, London WC1E 6JF, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Blair
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: B cell; Common variable immunodeficiency (CVID); Cytokine production; Flow cytometry; T cell