Evaluation of class switch recombination in B lymphocytes of patients with common variable immunodeficiency

Abstract

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders characterized by hypogammaglobulinemia and recurrent bacterial infections. Impaired antibody production in these patients is due to defect in B-cell differentiation into specific plasma cells. Class switch recombination (CSR), which plays a critical role in the production of different immunoglobulin isotypes, may be defective in a group of CVID patients. The aim of this study was to investigate the CSR process in B cells of CVID patients, by evaluating the expression of IgE mRNA and production of its protein in an IgE inductive medium. Peripheral blood mononuclear cells (PBMCs) from 29 CVID patients and 21 healthy controls were isolated and cultured in the presence of rhIL-4 and CD40L. IgE mRNA and IgE protein were measured by RT-PCR and ELISA techniques, respectively. Normal production of IgE mRNA was recorded in 23 out of 29 patients (79.31%) as well as all controls; while the remaining 6 patients (20.69%) were unable to express IgE mRNA indicating a defect in CSR. PBMCs of 16 out of 29 patients (55.2%) could not produce normal amounts of IgE compared with controls, after being stimulated by IL-4 and CD40L. Post B cell stimulation IgE production was impaired in about half of studied CVID patients. Defects in processes occur following the CSR process such as IgE mRNA transcription, protein production, and secretion can be the causative mechanism of CVID in patients with normal mRNA expression of the immunoglobulin but impaired protein production. Determination of these defects can help to clarify the various underlying mechanisms responsible for the development of CVID.