title: IL-10-driven immunoglobulin production by B lymphocytes from IgA-deficient individuals correlates to infection proneness.
abstract: In search for a possible explanation of the phenotypic heterogeneity in IgA deficiency, we studied the function of B cells from IgA-deficient (IgAd) individuals. Two groups of IgAd individuals, one frequently infected and one clinically apparently healthy, as well as normal controls, were studied. Peripheral blood mononuclear cells (PBMC) and B cells from IgAd individuals and controls were cultured with Staphylococcus aureus Cowan I strain and with anti-CD40 MoAb presented on the CD32-transfected fibroblast cell line in the presence of IL-10. In this experimental system PBMC and B cells from the infection-prone IgAd individuals produced only minute amounts of IgA. In contrast, PBMC and B cells from healthy IgAd subjects secreted significantly more IgA1 and IgA2 in comparison with infection-prone IgAd patients (P < 0.05). These data suggest that the abnormalities of B cell differentiation in IgAd could be of heterogeneous origin. Thus, whereas in healthy IgAd subjects IgA production may be efficiently up-regulated in vitro by addition of IL-10 to CD40-activated B cell culture, the corresponding B cell differentiation does not occur in infection-prone IgAd patients. These observations provide a conceptual framework for phenotypic heterogeneity in IgAd subjects.
authors.affiliation: Department of Clinical Immunology, Göteborg University, Sweden.
authors.forename: V
authors.initials: V
authors.lastname: Friman
authors.forename: L A
authors.initials: LA
authors.lastname: Hanson
authors.forename: J M
authors.initials: JM
authors.lastname: Bridon
authors.forename: A
authors.initials: A
authors.lastname: Tarkowski
authors.forename: J
authors.initials: J
authors.lastname: Banchereau
authors.forename: F
authors.initials: F
authors.lastname: Brière
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003470:Culture Media / Q000032:analysis; D004406:Dysgammaglobulinemia / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts; D006801:Humans; D017098:IgA Deficiency / Q000276:immunology*; D007070:Immunoglobulin A / Q000032:analysis / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000032:analysis / Q000096:biosynthesis; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology; D012141:Respiratory Tract Infections / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology; D013211:Staphylococcus aureus; D014162:Transfection; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D003470:Culture Media; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011994:Recombinant Proteins; D016753:Interleukin-10