title: B cells from nuclear factor kB essential modulator deficient patients fail to differentiate to antibody secreting cells in response to TLR9 ligand.
abstract: Hypohidrotic ectodermal dysplasia (HED) consists of disorders resulting from molecular alterations of ectodysplasin-A (EDA) pathway. Hypomorphic mutations in NF-kB essential modulator, downstream EDA, result in HED with immunodeficiency (HED-ID), characterized by susceptibility to encapsulated pyogenic bacteria infections. Increased susceptibility to pneumococcal infections and poor response to polysaccharide antigens are associated with defect in T-independent B-cell immunity. We investigated B-cell differentiation and immunoglobulin secretion induced by the TLR9 ligand CpG in two HED-ID and in a HED patient caused by EDA mutations (XLHED). In HED-ID, only few B cells differentiated into plasma cells upon TLR9 stimulation and memory B cells did not produce IgG and IgA, but small amounts of IgM. Unexpectedly, memory B cells from XLHED patient failed to produce normal IgA or IgG amount upon TLR9 stimulation. Our findings expand the knowledge about the pathogenesis of humoral alterations in HED patients and help explain the susceptibility to pneumococcal infections.
authors: Department of Translational Medical Sciences, Federico II University, Naples, Italy.
authors: Giuliana
authors: G
authors: Giardino
authors: Department of Translational Medical Sciences, Federico II University, Naples, Italy.
authors: Emilia
authors: E
authors: Cirillo
authors: Department of Translational Medical Sciences, Federico II University, Naples, Italy.
authors: Vera
authors: V
authors: Gallo
authors: Department of Translational Medical Sciences, Federico II University, Naples, Italy.
authors: Tiziana
authors: T
authors: Esposito
authors: International Institute of Genetics and Biophysics, IGB-CNR, Naples, Italy.
authors: Francesca
authors: F
authors: Fusco
authors: International Institute of Genetics and Biophysics, IGB-CNR, Naples, Italy.
authors: Matilde Immacolata
authors: MI
authors: Conte
authors: Department of Molecular Medicine, La Sapienza University, Rome, Italy.
authors: Isabella
authors: I
authors: Quinti
authors: International Institute of Genetics and Biophysics, IGB-CNR, Naples, Italy.
authors: Matilde Valeria
authors: MV
authors: Ursini
authors: Research Center, Ospedale Pediatrico Bambino Gesù (IRCCS), Rome, Italy.
authors: Rita
authors: R
authors: Carsetti
authors: Department of Translational Medical Sciences, Federico II University, Naples, Italy. Electronic address: pignata@unina.it.
authors: Claudio
authors: C
authors: Pignata
mesh_terms: D000921:Antibody-Producing Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility / Q000276:immunology; D053358:Ectodermal Dysplasia 1, Anhidrotic / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D008024:Ligands; D008297:Male; D016328:NF-kappa B / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology*
chemical_list: D007136:Immunoglobulins; D008024:Ligands; D016328:NF-kappa B; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9
keywords: CpG; Encapsulated bacteria; IgM memory B cell; NEMO; Nuclear factor kB essential modulator; TLR9