B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers

Langelaar, Jamie van; Rijvers, Liza; Smolders, Joost; Luijn, Marvin M. van

doi:10.3389/fimmu.2020.00760

Cited by 189 publications

(159 citation statements)

References 164 publications

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“…CD20 is a surface molecule present throughout the maturation cycle of B cells, from pre-B cells to memory cells, but not expressed on plasma cells (19). This discrepancy has caused a surge in the study of the antigen presentation ability of B cells (19)(20)(21)(22)(23)(24). Previously, our lab described an experimental model that largely mimics MS symptoms (25).…”

Section: Introductionmentioning

confidence: 99%

Multiple Sclerosis-Like Symptoms in Mice Are Driven by Latent γHerpesvirus-68 Infected B Cells

2020

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Multiple sclerosis (MS) is caused by a combination of genetic and environmental factors. It is believed that previous infection with Epstein Barr Virus (EBV) plays an important role in the development of MS. Previously, we developed a murine model where latent infection with gamma herpesvirus 68 (γHV-68), a murine homolog to EBV, enhanced the symptoms of experimental autoimmune encephalomyelitis (EAE), resulting in disease that more closely resembles MS in humans. Here, we explored the conditions that were necessary for EAE enhancement. We showed that latently infected CD19+IgD− B cells were capable of enhancing EAE symptoms when transferred from mice previously infected with γHV-68 into uninfected mice. We also observed a prevention of enhancement when B cells were depleted before infection. However, depletion after the establishment of latency only partially reduced EAE. This indicated the existence of a mechanism where B cells play an important role as antigen presenting cells (APCs) prior to EAE induction for the priming of Th1 cells. It is possible that these signals persist even after B cell depletion, strongly suggesting a paracrine signaling modulation of non-B cell APCs. These results strongly support the concept that EBV contributes to the development of autoimmunity and highlights the need for a vaccine against EBV that could limit or prevent multiple sclerosis development.

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Section: Introductionmentioning

confidence: 99%

Multiple Sclerosis-Like Symptoms in Mice Are Driven by Latent γHerpesvirus-68 Infected B Cells

2020

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“…MS is a chronic immune-mediated disease of the CNS whose pathological hallmark is focal demyelination associated with various degrees of neurodegeneration [37]. Complex immunological dysfunction-involving peripheral T and B lymphocytes and resident CNS immune cells-represents the immunological substrate for MS development and progression [38]. The intermittent aberrant activation of self-reacting immune cell subsets results in their transmigration across the BBB into the CNS, where they induce demyelinating and, ultimately, neuronal damage manifesting as clinical relapse and disability accumulation.…”

Section: Multiple Sclerosismentioning

confidence: 99%

COVID-19: dealing with a potential risk factor for chronic neurological disorders

Schirinzi

Landi²,

Liguori

2020

J Neurol

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SARS-CoV2 infection is responsible for a complex clinical syndrome, named Coronavirus Disease 2019 (COVID-19), whose main consequences are severe pneumonia and acute respiratory distress syndrome. Occurrence of acute and subacute neurological manifestations (encephalitis, stroke, headache, seizures, Guillain-Barrè syndrome) is increasingly reported in patients with COVID-19. Moreover, SARS-CoV2 immunopathology and tissue colonization in the gut and the central nervous system, and the systemic inflammatory response during COVID-19 may potentially trigger chronic autoimmune and neurodegenerative disorders. Specifically, Parkinson's disease, multiple sclerosis and narcolepsy present several pathogenic mechanisms that can be hypothetically initiated by SARS-CoV2 infection in susceptible individuals. In this short narrative review, we summarize the clinical evidence supporting the rationale for investigating SARS-CoV2 infection as risk factor for these neurological disorders, and suggest the opportunity to perform in the future SARS-CoV2 serology when diagnosing these disorders.

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“…Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS) characterised by episodes of inflammation that result in demyelination. A number of risk factors for MS have been identified ( 1 ), but the specific mechanisms of immune-mediated demyelination require further investigation ( 2 ). In and around MS lesions, there is evidence of infiltrating immune cells, an inflammatory cytokine milieu and deposits of immunoglobulins (Ig) and complement ( 3 – 5 ).…”

Section: Introductionmentioning

confidence: 99%

FcγRIIb Expression Is Decreased on Naive and Marginal Zone-Like B Cells From Females With Multiple Sclerosis

et al. 2021

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B cells are critical to the development of multiple sclerosis (MS), but the mechanisms by which they contribute to the disease are poorly defined. We hypothesised that the expression of CD32b (FcγRIIb), a receptor for the Fc region of IgG with inhibitory activities in B cells, is lower on B cell subsets from people with clinically isolated syndrome (CIS) or MS. CD32b expression was highest on post-naive IgM+ B cell subsets in healthy controls. For females with MS or CIS, significantly lower CD32b expression was identified on IgM+ B cell subsets, including naive and IgMhi MZ-like B cells, when compared with control females. Lower CD32b expression on these B cell subsets was associated with detectable anti-Epstein Barr Virus viral capsid antigen IgM antibodies, and higher serum levels of B cell activating factor. To investigate the effects of lower CD32b expression, B cells were polyclonally activated in the presence of IgG immune complexes, with or without a CD32b blocking antibody, and the expression of TNF and IL-10 in B cell subsets was assessed. The reduction of TNF but not IL-10 expression in controls mediated by IgG immune complexes was reversed by CD32b blockade in naive and IgMhi MZ-like B cells only. However, no consequence of lower CD32b expression on these cells from females with CIS or MS was detected. Our findings highlight a potential role for naive and marginal zone-like B cells in the immunopathogenesis of MS in females, which requires further investigation.

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B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers

Cited by 189 publications

References 164 publications

Multiple Sclerosis-Like Symptoms in Mice Are Driven by Latent γHerpesvirus-68 Infected B Cells

Multiple Sclerosis-Like Symptoms in Mice Are Driven by Latent γHerpesvirus-68 Infected B Cells

COVID-19: dealing with a potential risk factor for chronic neurological disorders

FcγRIIb Expression Is Decreased on Naive and Marginal Zone-Like B Cells From Females With Multiple Sclerosis

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