Contribution of B-lymphocytes to the production of Interleukin-17 in multiple sclerosis

Abstract

The study of pathogenic systems involved in multiple sclerosis (MS) is essential for the development of new therapies.Objective: to determine the contribution of B-lymphocytes to the production of IL-17 in MS with an assessment of the ability of B-cells to induce the differentiation of Th17 and the own production of IL-17 by B-lymphocytes in this pathology.Material and methods. A total of 81 subjects were examined, 68 of whom were patients diagnosed with MS, 13 were healthy individuals. The concentrations of IL-17A, IL-10, BAFF and total IgG were analyzed in blood serum by ELISA. The additional study included 13 MS patients and 11 healthy donors. Mononuclear cells were isolated from the blood, from which B-lymphocytes and CD4+T-lymphocytes were obtained. B-lymphocytes were incubated with tetanus toxoid or with myelin-oligodendrocyte glycoprotein (MOG), after which they were washed from unbounded antigen and cultured together with autologous CD4+T-lymphocytes or with peripheral blood mononuclear cells, then the content of Th17 cells in the sample was evaluated. Flow cytometry ex vivo assessed the expression of RORγt by B-lymphocytes and CD4+T-lymphocytes. The level of IL-17 in blood serum and cell culture supernatants was determined by ELISA.Results. High IL-17 serum levels in MS patients are associated with elevated BAFF concentrations, and in patients with high IgG levels, IL-17 concentrations were also twice as high. A statistically significant higher level of IL-17-positive B-lymphocytes was detected in MS.Conclusion. B-lymphocytes may contribute to the production of IL-17 in MS in two ways – by inducing the differentiation of T-lymphocytes producing this cytokine and by their own synthesis of IL-17.