Deep cervical lymph nodes of patients with multiple sclerosis show dysregulated B cells in the presence of Epstein-Barr virus

Abstract

Despite the recognized role of Epstein-Barr virus (EBV) in predisposing to multiple sclerosis (MS) and the effectiveness of B cell-depleting therapies in MS, the mechanism of autoimmunity remains elusive. Using fine needle aspirations, we investigated deep cervical lymph nodes (dcLNs), the primary site of the adaptive immune response against EBV, in newly diagnosed untreated MS patients and healthy controls. We characterized the immune landscape of dcLNs with scRNAseq and CITE-seq and observed increased memory B cell proportions and reduced germinal center (GC) B cells with decreased clonality in patients with MS compared to healthy controls. In the patient with an active MS relapse, we detected elevated plasmablasts, reduced GC B cells, and clonally expanded memory CD8 T cells targeting EBV in the dcLN. These findings, along with increased EBV DNA detection in dcLNs and viral loads in patient saliva, support B cell dysregulation as a key mechanism in MS pathogenesis.