Circulating Memory B Cells in Early Multiple Sclerosis Exhibit Increased IgA + Cells, Globally Decreased BAFF-R Expression and an EBV-Related IgM + Cell Signature.

Autor:	Leffler J; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia., Trend S; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.; Centre for Neuromuscular and Neurological Disorders, Perron Institute for Neurological and Translational Science, University of Western Australia, Perth, WA, Australia., Ward NC; Dobney Hypertension Centre, Medical School, University of Western Australia, Perth, WA, Australia., Grau GE; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia., Hawke S; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia., Byrne SN; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.; Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, Westmead, NSW, Australia., Kermode AG; Centre for Neuromuscular and Neurological Disorders, Perron Institute for Neurological and Translational Science, University of Western Australia, Perth, WA, Australia.; Institute for Immunology and Infectious Disease, Murdoch University, Perth, WA, Australia., French MA; School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia.; Immunology Division, PathWest Laboratory Medicine, Perth, WA, Australia., Hart PH; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Feb 16; Vol. 13, pp. 812317. Date of Electronic Publication: 2022 Feb 16 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.812317
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Leffler, Trend, Ward, Grau, Hawke, Byrne, Kermode, French and Hart.)
Databáze:	MEDLINE
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