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Dynamic alterations of dural and bone marrow B cells in an animal model of progressive multiple sclerosis
Alexandra Florescu1, Michelle Zuo1, Angela A Wang1
1Department of Immunology, University of Toronto, Toronto, Canada.
Abstract:
In 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 B220high B 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 B220low B 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 B220low B cells at the expense of class-switched B220high B cells accompanied by severe, chronic disease. In summary, dynamic changes in the brain, LM, and dural B cells are associated with age-dependent disease severity in an animal model of progressive MS.
Insights
In multiple sclerosis (MS), immune cells in the brain's leptomeninges (LM) differ with age. Aged mice show more severe disease due to altered B cell populations in the brain and dura.
Area of Science:
- Neuroimmunology
- Immunology
- Neurology
Background:
- Immune cell aggregates in the leptomeninges (LM) are characteristic of multiple sclerosis (MS) and linked to disease progression.
- The specific role and impact of LM inflammation on the adjacent dura mater in MS pathogenesis remain largely unexplored.
Purpose of the Study:
- To investigate the impact of LM inflammation on the adjacent dura in a mouse model of MS.
- To analyze the dynamic changes in B cell populations within the brain, LM, and dura in relation to age-dependent disease severity.
Main Methods:
- Utilized a mouse model of MS exhibiting brain LM inflammation and age-dependent disease progression.
- Analyzed immune cell infiltration, specifically T cells and B cell subsets (B220high and B220low), in the brain, LM, and dura.
- Correlated B cell populations with disease onset, remission, and severity in young versus aged mice.
Main Results:
- Encephalitogenic T cells and B220high B cells accumulated in the brain LM and parenchyma of both young and aged mice.
- The dura remained relatively unaffected, but contained a distinct population of anti-CD20-resistant B220low B cells.
- Aged mice exhibited a decrease in brain-resident B220low B cells and an increase in class-switched B220high B cells, correlating with severe, chronic disease.
Conclusions:
- Dynamic alterations in B cell populations within the brain, LM, and dura are associated with age-dependent MS severity.
- The balance between B220low and B220high B cells in the central nervous system compartments may influence disease progression and chronicity in MS.
