IL-10-Producing Regulatory B Cells Are Decreased in Patients with Common Variable Immunodeficiency.

Nathalia Silveira Barsotti,Priscilla Ramos Costa,Cristina Maria Kokron,Jorge Kalil,Rafael Ribeiro Almeida,Myrthes Toledo Barros

doi:10.1371/journal.pone.0151761

Nathalia Silveira Barsotti, Priscilla Ramos Costa + Show 4 more

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https://doi.org/10.1371/journal.pone.0151761

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Journal: PloS one	Publication Date: Mar 18, 2016
Citations: 33	License type: CC BY 4.0

Affiliation: Universidade de São Paulo

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.

Highlights

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency in adults, characterized by hypogammaglobulinemia and defective antibody responses
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
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

Summary

Introduction

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency in adults, characterized by hypogammaglobulinemia and defective antibody responses. Malignancy, chronic gastroenteropathies and autoimmunity are often present. Numerous cellular dysfunctions are present in CVID comprising both T and B cells, which suggest combined immune defects. Decreased frequency of naïve T cells and Treg cells, increased chronic activated T cells [7,8,9] and altered cytokine production [10, 11] are some of the defects related to CVID. Recent reports have shown that chronic T cell activation is related to microbial translocation and increased levels of plasma sCD14 [11, 12]. Most of CVID patients have normal or slightly reduced frequency of CD19+ B cells [7, 13]

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