title: B cells from common variable immunodeficiency patients fail to differentiate to antibody secreting cells in response to TLR9 ligand (CpG-ODN) or anti-CD40+IL21.
abstract: Common variable immunodeficiency (CVID) is a primary immunodeficiency characterised by hypogammaglobulinaemia and antibody deficiency to T dependent and independent antigens. Patients suffer from recurrent respiratory infections and poor response to vaccination. Although the underlying molecular defect is unknown, most CVID patients show impaired late B cell differentiation. We investigated B cell differentiation and immunoglobulin secretion induced by two different stimuli: TLR9 specific ligand (CpG-ODN) and anti-CD40 combined with IL21. The contribution of BCR signalling (anti-IgM stimulation) was also evaluated. B cells from CVID patients produced low levels of IgG and IgA in response to both kinds of stimuli that was not restored by anti-IgM. Production of IgM was conserved when cells were stimulated with anti-CD40 and IL21. These results point to a wide signalling defect in B lymphocytes from CVID patients that may be related to their hypogammaglobulinaemia and poor response to vaccination.
authors.affiliation: Servei d'Immunologia, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Hospital Son Dureta, Palma de Mallorca, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Clemente
authors.forename: Jaime
authors.initials: J
authors.lastname: Pons
authors.forename: Nuria
authors.initials: N
authors.lastname: Matamoros
authors.forename: Julio
authors.initials: J
authors.lastname: Iglesias
authors.forename: Joana M
authors.initials: JM
authors.lastname: Ferrer
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D000921:Antibody-Producing Cells / Q000166:cytology / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects*; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D007378:Interleukins / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D051217:Toll-Like Receptor 9 / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D000906:Antibodies; C408982:CPG-oligonucleotide; D007136:Immunoglobulins; D007378:Interleukins; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D023201:CD40 Ligand; D000098546:Interleukin-21