CD11c+ B cells in relapsing–remitting multiple sclerosis and effects of anti‐CD20 therapy

Abstract

Abstract Objectives B cells are important in the pathogenesis of multiple sclerosis. It is yet unknown which subsets may be involved, but atypical B cells have been proposed as mediators of autoimmunity. In this study, we investigated differences in B‐cell subsets between controls and patients with untreated and anti‐CD20‐treated multiple sclerosis. Methods We recruited 155 participants for an exploratory cohort comprising peripheral blood and cerebrospinal fluid, and a validation cohort comprising peripheral blood. Flow cytometry was used to characterize B‐cell phenotypes and effector functions of CD11c+ atypical B cells. Results There were no differences in circulating B cells between controls and untreated multiple sclerosis. As expected, anti‐CD20‐treated patients had a markedly lower B‐cell count. Of B cells remaining after treatment, we observed higher proportions of CD11c+ B cells and plasmablasts. CD11c+ B cells were expanded in cerebrospinal fluid compared to peripheral blood in controls and untreated multiple sclerosis. Surprisingly, the proportion of CD11c+ cerebrospinal fluid B cells was higher in controls and after anti‐CD20 therapy than in untreated multiple sclerosis. Apart from the presence of plasmablasts, the cerebrospinal fluid B‐cell composition after anti‐CD20 therapy resembled that of controls. CD11c+ B cells demonstrated a high potential for both proinflammatory and regulatory cytokine production. Interpretation The study demonstrates that CD11c+ B cells and plasmablasts are less efficiently depleted by anti‐CD20 therapy, and that CD11c+ B cells comprise a phenotypically and functionally distinct, albeit heterogenous, B‐cell subset with the capacity of exerting both proinflammatory and regulatory functions.