title: IL-10-Producing Regulatory B Cells Are Decreased in Patients with Common Variable Immunodeficiency.
abstract: Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency in adults. CVID patients often present changes in the frequency and function of B lymphocytes, reduced number of Treg cells, chronic immune activation, recurrent infections, high incidence of autoimmunity and increased risk for malignancies. We hypothesized that the frequency of B10 cells would be diminished in CVID patients because these cells play an important role in the development of Treg cells and in the control of T cell activation and autoimmunity. Therefore, we evaluated the frequency of B10 cells in CVID patients and correlated it with different clinical and immunological characteristics of this disease. Forty-two CVID patients and 17 healthy controls were recruited for this study. Cryopreserved PBMCs were used for analysis of T cell activation, frequency of Treg cells and characterization of B10 cells by flow cytometry. IL-10 production by sorted B cells culture and plasma sCD14 were determined by ELISA. We found that CVID patients presented decreased frequency of IL-10-producing CD24hiCD38hi B cells in different cell culture conditions and decreased frequency of IL-10-producing CD24hiCD27+ B cells stimulated with CpG+PIB. Moreover, we found that CVID patients presented lower secretion of IL-10 by sorting-purified B cells when compared to healthy controls. The frequency of B10 cells had no correlation with autoimmunity, immune activation and Treg cells in CVID patients. This work suggests that CVID patients have a compromised regulatory B cell compartment which is not correlated with clinical and immunological characteristics presented by these individuals.
authors.affiliation: Laboratory of Clinical Immunology and Allergy-LIM60, Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Nathalia Silveira
authors.initials: NS
authors.lastname: Barsotti
authors.affiliation: Laboratory of Clinical Immunology and Allergy-LIM60, Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Rafael Ribeiro
authors.initials: RR
authors.lastname: Almeida
authors.affiliation: Laboratory of Clinical Immunology and Allergy-LIM60, Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Priscilla Ramos
authors.initials: PR
authors.lastname: Costa
authors.affiliation: Institute for Investigation in Immunology-INCT, São Paulo, Brazil.|Primary Immunodeficiency Outpatient Clinic of Clinical Immunology and Allergy Division of HC-FMUSP, São Paulo, Brazil.
authors.forename: Myrthes Toledo
authors.initials: MT
authors.lastname: Barros
authors.affiliation: Laboratory of Clinical Immunology and Allergy-LIM60, Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.|Institute for Investigation in Immunology-INCT, São Paulo, Brazil.|Heart Institute, (InCor), University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.affiliation: Laboratory of Clinical Immunology and Allergy-LIM60, Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.|Institute for Investigation in Immunology-INCT, São Paulo, Brazil.|Primary Immunodeficiency Outpatient Clinic of Clinical Immunology and Allergy Division of HC-FMUSP, São Paulo, Brazil.
authors.forename: Cristina Maria
authors.initials: CM
authors.lastname: Kokron
mesh_terms: D015551:Autoimmunity; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D017074:Common Variable Immunodeficiency / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D008213:Lymphocyte Activation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D016753:Interleukin-10