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Circulating memory B Cells in early Multiple Sclerosis exhibit increased IgA+ Cells, globally decreased BAFF-R expression and an EBV-related IgM+ cell signature

Leffler, J., Trend, S., Ward, N.C., Grau, G.E., Hawke, S., Byrne, S.N., Kermode, A.G., French, M.A. and Hart, P.H. (2022) Circulating memory B Cells in early Multiple Sclerosis exhibit increased IgA+ Cells, globally decreased BAFF-R expression and an EBV-related IgM+ cell signature. Frontiers in Immunology, 13 . Art. 812317.

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Abstract

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.

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: Frontiers Media
Copyright: © 2022 Leffler et al.
United Nations SDGs: Goal 3: Good Health and Well-Being
URI: http://researchrepository.murdoch.edu.au/id/eprint/64134
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