B cells in autoimmune and neurodegenerative central nervous system diseases

Sabatino, Joseph J.; Pröbstel, Anne-Katrin; Zamvil, Scott S.

doi:10.1038/s41583-019-0233-2

Cited by 214 publications

(206 citation statements)

References 317 publications

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“…B cells and plasma cells are virtually absent from the CP B cells are implicated in the pathogenesis of progressive MS, as demonstrated by the efficacy of CD20-targeted therapies [7,8,13,25]. In the meninges, B cells and plasma cells are present in the follicle-like structures found in some progressive MS patients [22,26], and there are more B cells in the CSF of progressive MS patients relative to controls [10].…”

Section: -Test) G Lack Of Correlation Between Interacting T Cells Anmentioning

confidence: 99%

Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells

Rodríguez‐Lorenzo

Konings

Pol

et al. 2020

acta neuropathol commun

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The choroid plexus (CP) is strategically located between the peripheral blood and the cerebrospinal fluid, and is involved in the regulation of central nervous system (CNS) homeostasis. In multiple sclerosis (MS), demyelination and inflammation occur in the CNS. While experimental animal models of MS pointed to the CP as a key route for immune cell invasion of the CNS, little is known about the distribution of immune cells in the human CP during progressive phases of MS. Here, we use immunohistochemistry and confocal microscopy to explore the main immune cell populations in the CP of progressive MS patients and non-neuroinflammatory controls, in terms of abundance and location within the distinct CP compartments. We show for the first time that the CP stromal density of granulocytes and CD8+ T cells is higher in progressive MS patients compared to controls. In line with previous studies, the CP of both controls and progressive MS patients contains relatively high numbers of macrophages and dendritic cells. Moreover, we found virtually no B cells or plasma cells in the CP. MHCII+ antigenpresenting cells were often found in close proximity to T cells, suggesting constitutive CNS immune monitoring functions of the CP. Together, our data highlights the role of the CP in immune homeostasis and indicates the occurrence of mild inflammatory processes in the CP of progressive MS patients. However, our findings suggest that the CP is only marginally involved in immune cell migration into the CNS in chronic MS.

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Section: -Test) G Lack Of Correlation Between Interacting T Cells Anmentioning

confidence: 99%

Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells

Rodríguez‐Lorenzo

Konings

Pol

et al. 2020

acta neuropathol commun

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“…As a control experiment for the reconstitution of T cells, we reconstituted a different group of NSG mice with B cells (timeline of experiment represented in Figure 4a). Since B cells on their own are not expected to affect pathology as they need T cells to work in concert for an antibody response [52,53], we used this experiment as a control to determine the effect of the reconstitution per se. The transfer of B cells was confirmed by flow cytometry (Figure 4b , supplementary Tables 3 and 4).…”

Section: Decreased Phosphorylated α-Syn In Nsg Mice Reconstituted Witmentioning

confidence: 99%

T cells limit accumulation of aggregate pathology following intrastriatal injection of α-synuclein fibrils

George¹,

Tyson²,

Rey

et al. 2020

Preprint

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α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of αsynucleinopathies, such as Parkinson's disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells.These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease.To study the role of the adaptive immune system with respect to α-syn pathology, we injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology as well as microgliosis. Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. We also reconstituted T and B cell populations in the NSG mice with cells isolated from a wildtype mouse spleen. Interestingly, reconstituting the T cell population decreased the accumulation of α-syn pathology and resulted in persistent microgliosis when compared to non-transplanted mice; reconstitution of B cells did not alter the nigral neuropathology. Our work provides experimental evidence that T cells play a role in the pathogenesis of α-synucleinopathies.

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“…The decreased number of B lymphocytes is also associated with alterations in the expression of B cell-related genes in peripheral blood leukocytes in PD patients ( Kobo et al, 2016 ). However, it is unclear whether the change in number or functionality of B lymphocytes are causal or secondary to CNS injury in PD ( Sabatino et al, 2019 ). Evaluation of T lymphocyte subsets showed a decrease in CD4 + T cells with an increase in CD8 + T cells ( Baba et al, 2005 ; Saunders et al, 2012 ; Stevens et al, 2012 ).…”

Section: Parkinson’s Diseasementioning

confidence: 99%

Aging and Neurodegenerative Disease: Is the Adaptive Immune System a Friend or Foe?

Mayne

White

McMurran

et al. 2020

Front. Aging Neurosci.

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Neurodegenerative diseases of the central nervous system (CNS) are characterized by progressive neuronal death and neurological dysfunction, leading to increased disability and a loss of cognitive or motor functions. Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis have neurodegeneration as a primary feature. However, in other CNS diseases such as multiple sclerosis, stroke, traumatic brain injury, and spinal cord injury, neurodegeneration follows another insult, such as demyelination or ischaemia. Although there are different primary causes to these diseases, they all share a hallmark of neuroinflammation. Neuroinflammation can occur through the activation of resident immune cells such as microglia, cells of the innate and adaptive peripheral immune system, meningeal inflammation and autoantibodies directed toward components of the CNS. Despite chronic inflammation being pathogenic in these diseases, local inflammation after insult can also promote endogenous regenerative processes in the CNS, which are key to slowing disease progression. The normal aging process in the healthy brain is associated with a decline in physiological function, a steady increase in levels of neuroinflammation, brain shrinkage, and memory deficits. Likewise, aging is also a key contributor to the progression and exacerbation of neurodegenerative diseases. As there are associated co-morbidities within an aging population, pinpointing the precise relationship between aging and neurodegenerative disease progression can be a challenge. The CNS has historically been considered an isolated, “immune privileged” site, however, there is mounting evidence that adaptive immune cells are present in the CNS of both healthy individuals and diseased patients. Adaptive immune cells have also been implicated in both the degeneration and regeneration of the CNS. In this review, we will discuss the key role of the adaptive immune system in CNS degeneration and regeneration, with a focus on how aging influences this crosstalk.

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B cells in autoimmune and neurodegenerative central nervous system diseases

Cited by 214 publications

References 317 publications

Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells

Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells

T cells limit accumulation of aggregate pathology following intrastriatal injection of α-synuclein fibrils

Aging and Neurodegenerative Disease: Is the Adaptive Immune System a Friend or Foe?

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