期刊
FRONTIERS IN IMMUNOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.812317
关键词
multiple sclerosis; B cells; memory B cells; IgA; BAFF; short chain fatty acids; Epstein Barr virus; flow cytometry
类别
资金
- MSWA
- MS Australia as well as the National Health and Medical Research Council of Australia [1067209]
This study investigates the role of B cells in multiple sclerosis (MS) and reveals that MS patients exhibit dysregulation in B cell homeostasis, including increased memory B cells and decreased expression of BAFF-R. The study also demonstrates that reactivation of Epstein Barr Virus (EBV) in MS patients is associated with phenotypic changes in B cells. These findings provide further insights into the pathological mechanisms of MS and the complex role of BAFF/BAFF-R signaling.
Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system that results in demyelination of axons, inefficient signal transmission and reduced muscular mobility. Recent findings suggest that B cells play a significant role in disease development and pathology. To further explore this, B cell profiles in peripheral blood from 28 treatment-naive patients with early MS were assessed using flow cytometry and compared to 17 healthy controls. Conventional and algorithm-based analysis revealed a significant increase in MS patients of IgA(+) memory B cells (MBC) including CD27(+), CD27(-) and Tbet(+) subsets. Screening circulating B cells for markers associated with B cell function revealed a significantly decreased expression of the B cell activation factor receptor (BAFF-R) in MS patients compared to controls. In healthy controls, BAFF-R expression was inversely associated with abundance of differentiated MBC but this was not observed in MS. Instead in MS patients, decreased BAFF-R expression correlated with increased production of proinflammatory TNF following B cell stimulation. Finally, we demonstrated that reactivation of Epstein Barr Virus (EBV) in MS patients was associated with several phenotypic changes amongst MBCs, particularly increased expression of HLA-DR molecules and markers of a T-bet(+) differentiation pathway in IgM(+) MBCs. Together, these data suggest that the B cell compartment is dysregulated in MS regarding aberrant MBC homeostasis, driven by reduced BAFF-R expression and EBV reactivation. This study adds further insights into the contribution of B cells to the pathological mechanisms of MS, as well as the complex role of BAFF/BAFF-R signalling in MS.
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