Dynamic alterations of dural and bone marrow B cells in an animal model of progressive multiple sclerosis

Abstract

AbstractIn multiple sclerosis (MS), the leptomeninges (LM) are populated with immune cell aggregates that correlate with disease progression. The impact of LM inflammation on the adjacent dura is largely unknown. Using a mouse model of MS that induces brain LM inflammation and age-dependent disease progression, we found that encephalitogenic T cells and B220highB cells accumulate substantially in the brain LM and parenchyma of both young and aged mice, while the adjacent dura remains relatively inert. We also observed a population of anti-CD20 resistant B220lowB cells in the dura and bone marrow that virtually disappear at disease onset and accumulate in the brain of young mice concomitant with disease remission. In contrast, aged mice show a paucity of brain-resident B220lowB cells at the expense of class-switched B220highB cells concomitant with severe, chronic disease. In summary, dynamic changes in brain, LM and dural B cells are associated with age-dependent disease severity in an animal model of progressive MS.Short SummaryFlorescuet al. investigate the temporal accumulation of immune cells within distinct meningeal compartments in an animal model of progressive MS and uncover a population of anti-CD20 resistant dural B cells that remain in the brain parenchyma at disease remission.