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Optic neuritis (ON) is one of the common first manifestations of multiple sclerosis (MS). Manuscript data demonstrates involvement of peripheral blood B-cell sub-population during the first episode of acute ON in MS patients. The findings approve a significant role of B lymphocytes in the pathogenesis of the first episode of acute ON. Research data and conclusions could be useful for core understanding of MS pathogenesis and would be successful application in clinical practice of early ON treatment.