2023
DOI: 10.21203/rs.3.rs-2398872/v1
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Unstable EBV latency drives inflammation in multiple sclerosis patient derived spontaneous B cells

Abstract: Epidemiological studies have demonstrated that Epstein-Barr virus (EBV) is a known etiologic risk factor, and perhaps prerequisite, for the development of MS. EBV establishes life-long latent infection in a subpopulation of memory B cells. Although the role of memory B cells in the pathobiology of MS is well established, studies characterizing EBV-associated mechanisms of B cell inflammation and disease pathogenesis in EBV (+) B cells from MS patients are limited. Accordingly, we analyzed spontaneous lymphobla… Show more

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Cited by 3 publications
(3 citation statements)
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“…Although EBV load is not significantly increased in the CSF and peripheral blood of MS patients compared to healthy controls, preliminary data point to unstable EBV latency and EBV reactivation in B-cells from MS patients, particularly during active disease. 10 Work of our and other groups in post-mortem MS brains suggests that EBV-harboring B-cells might establish a persistent pool of latently and lytically infected B-cells in the CNS that become the target of an antiviral cytotoxic immune response causing collateral tissue damage. 8 Because there is evidence for B-cell trafficking between blood and CNS and for B-cell activation in deep cervical lymph nodes of MS patients, CNS-draining lymphoid tissue might be the main site of EBV-antigen presentation by infected B-cells.…”
Section: Immunopathology Driven By Ebvmentioning
confidence: 78%
“…Although EBV load is not significantly increased in the CSF and peripheral blood of MS patients compared to healthy controls, preliminary data point to unstable EBV latency and EBV reactivation in B-cells from MS patients, particularly during active disease. 10 Work of our and other groups in post-mortem MS brains suggests that EBV-harboring B-cells might establish a persistent pool of latently and lytically infected B-cells in the CNS that become the target of an antiviral cytotoxic immune response causing collateral tissue damage. 8 Because there is evidence for B-cell trafficking between blood and CNS and for B-cell activation in deep cervical lymph nodes of MS patients, CNS-draining lymphoid tissue might be the main site of EBV-antigen presentation by infected B-cells.…”
Section: Immunopathology Driven By Ebvmentioning
confidence: 78%
“…A lack of differential expression of any HERV family was however unexpected given our original hypothesis that Ocrelizumab depletion of B cells would decrease the opportunity for viral expression in MS patients. This study does however offer support to the body of evidence that suggests that an aberrant cell type or immune response triggered by these viruses, rather than ongoing high viral expression, drives continued pathology in MS. Current evidence points strongly to an aberrant EBV latency programme and resulting in an expanded T-bet/CXCR3 + memory B cell population that is critical in MS pathology 63,68 .…”
Section: Discussionmentioning
confidence: 99%
“…Generation of spontaneous lymphoblastoid cell lines (transformed EBV infected B cells) is more common in MS patients (and in other autoimmune diseases) than in healthy controls 63,64 and genetic variation in EBV latency associated proteins 65 in MS patients has been demonstrated. Expression of the latency-associated protein, EBNA1, is enhanced in B cells from younger patients 16 while “age-associated” B cells (which are expanded in older patients) are also expanded in MS patients and altered based on herpesvirus status 66 .…”
Section: Introductionmentioning
confidence: 99%