title: Increased STAT3 phosphorylation on CD27(+) B-cells from common variable immunodeficiency disease patients.
abstract: Maturation and differentiation of B-cells are driven by T-cells' help through IL-21/STAT3 axis in GC centers or through extrafollicular pathways, in a T-independent manner. B-cell differentiation is defective in common variable immunodeficiency disease (CVID) patients. We investigated if IL-21/STAT3 axis alterations could influence B-cell fate. We activated purified CVID B-cells with surrogate T-dependent (anti-CD40), T-independent (TLR-9 ligand) stimuli or through B-cell receptor engagement (anti-IgM) with or without IL-21. IL-21 mediated STAT3 activation was greater on CD27(-) than CD27(+) B-cells depending on the stimulus. IL-21 alone induced STAT3 phosphorylation (pSTAT3) only on CD27(-) B-cells and IL-21 induced higher pSTAT3 levels on CD27(-) than CD27(+) B-cells after anti-IgM or anti-CD40 activation. CVID CD27(+) B-cells showed selective STAT3 hyperphosphorylation after activation with anti-IgM or anti-CD40 alone and anti-IgM, anti-CD40 or ODN combined with IL-21. Increased STAT3 activation during immune responses could result in B-cell differentiation defects in CVID.
authors.affiliation: Fundació d'Investigació Sanitària de les Illes Balears (FISIB), Hospital Universitari Son Espases, Palma de Mallorca, Spain; Institut d'Investigació Sanitària de Palma (IdISPa), Hospital Universitari Son Espases, Palma de Mallorca, Spain. Electronic address: ACLEMENTE@clinic.ub.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Clemente
authors.affiliation: Institut d'Investigació Sanitària de Palma (IdISPa), Hospital Universitari Son Espases, Palma de Mallorca, Spain; Immunology Department, Hospital Universitari Son Espases, Palma de Mallorca, Spain. Electronic address: jaime.pons@ssib.es.
authors.forename: Jaume
authors.initials: J
authors.lastname: Pons
authors.affiliation: Institut d'Investigació Sanitària de Palma (IdISPa), Hospital Universitari Son Espases, Palma de Mallorca, Spain; Immunology Department, Hospital Universitari Son Espases, Palma de Mallorca, Spain. Electronic address: nallibe.lanio@ssib.es.
authors.forename: Nallibe
authors.initials: N
authors.lastname: Lanio
authors.affiliation: Institut d'Investigació Sanitària de Palma (IdISPa), Hospital Universitari Son Espases, Palma de Mallorca, Spain; Immunology Department, Hospital Universitari Son Espases, Palma de Mallorca, Spain. Electronic address: vanesa.cunill@ssib.es.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Cunill
authors.affiliation: Unitat d'Investigació, Hospital Universitari Son Espases, Palma de Mallorca, Spain. Electronic address: guillem.frontera@ssib.es.
authors.forename: Guillem
authors.initials: G
authors.lastname: Frontera
authors.affiliation: Unitat d'Investigació, Hospital Universitari Son Espases, Palma de Mallorca, Spain. Electronic address: catalina.crespib@ssib.es.
authors.forename: Catalina
authors.initials: C
authors.lastname: Crespí
authors.affiliation: Institut d'Investigació Sanitària de Palma (IdISPa), Hospital Universitari Son Espases, Palma de Mallorca, Spain; Immunology Department, Hospital Universitari Son Espases, Palma de Mallorca, Spain. Electronic address: nuria.matamoros@ssib.es.
authors.forename: Núria
authors.initials: N
authors.lastname: Matamoros
authors.affiliation: Institut d'Investigació Sanitària de Palma (IdISPa), Hospital Universitari Son Espases, Palma de Mallorca, Spain; Immunology Department, Hospital Universitari Son Espases, Palma de Mallorca, Spain. Electronic address: juanam.ferrer@ssib.es.
authors.forename: Joana M
authors.initials: JM
authors.lastname: Ferrer
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D010766:Phosphorylation / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D000888:Antibodies, Anti-Idiotypic; D019013:CD40 Antigens; D007378:Interleukins; D011947:Receptors, Antigen, B-Cell; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C044203:anti-IgM; D000098546:Interleukin-21
keywords: B-cells; BCR; CD40; CVID; IL-21 co-stimulation; STAT3; TLR-9