Journal article
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, Vol.13, Art. 812317
2022
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.
Details
- Title
- Circulating memory B Cells in early Multiple Sclerosis exhibit increased IgA+ Cells, globally decreased BAFF-R expression and an EBV-related IgM+ cell signature
- Authors/Creators
- J. Leffler (Author/Creator) - The Kids Research Institute AustraliaS. Trend (Author/Creator) - The Kids Research Institute AustraliaN.C. Ward (Author/Creator) - The University of Western AustraliaG.E. Grau (Author/Creator) - The University of SydneyS. Hawke (Author/Creator) - The University of SydneyS.N. Byrne (Author/Creator) - The University of SydneyA.G. Kermode (Author/Creator) - Perron Institute for Neurological and Translational ScienceM.A. French (Author/Creator) - The University of Western AustraliaP.H. Hart (Author/Creator) - The Kids Research Institute Australia
- Publication Details
- Frontiers in Immunology, Vol.13, Art. 812317
- Publisher
- Frontiers Media
- Identifiers
- 991005540717407891
- Copyright
- © 2022 Leffler et al.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.203 Neuromuscular Disorders
- 1.203.147 Multiple Sclerosis
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology