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B cells in autoimmune and neurodegenerative central nervous system diseases

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From Nature Reviews Neuroscience

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A Publisher Correction to this article was published on 26 November 2019

Abstract

B cells are essential components of the adaptive immune system and have important roles in the pathogenesis of several central nervous system (CNS) diseases. Besides producing antibodies, B cells perform other functions, including antigen presentation to T cells, production of proinflammatory cytokines and secretion of anti-inflammatory cytokines that limit immune responses. B cells can contribute to CNS disease either through their actions in the periphery (meaning that they have an ‘outside-in’ effect on CNS immunopathology) or following their compartmentalization within the CNS. The success of B cell-depleting therapy in patients with multiple sclerosis and CNS diseases with an autoantibody component, such as neuromyelitis optica spectrum disorder and autoimmune encephalitides, has underscored the role of B cells in both cellular and humoral-mediated CNS conditions. Emerging evidence suggests B cells also contribute to the pathogenesis of neurodegenerative diseases, including Alzheimer disease and Parkinson disease. Advancing our understanding of the role of B cells in neuroinflammatory and neurodegenerative diseases could lead to novel therapeutic approaches.

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Fig. 1: B cell lineages and functions.
Fig. 2: B cells in the immunopathogenesis of multiple sclerosis (MS).
Fig. 3: B cell-mediated pathogenesis of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease.
Fig. 4: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis.
Fig. 5: Potential roles for B cells in neurodegenerative disorders.

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Acknowledgements

J.J.S. is supported by research grants from the US National Institutes of Health (1K08NS107619-01A1), the US National Multiple Sclerosis Society (TA-1903-33713) and the Race to Erase MS. A.-K.P. is supported by postdoctoral fellowships from the Swiss National Science Foundation (P2SKP3_164938/1 and P300PB_177927/1) and the US National Multiple Sclerosis Society (Kathleen C. Moore Fellowship, FG-1708-28871). S.S.Z. is supported by research grants from the US National Institutes of Health (1 RO1 NS092835-01, 1 R01 AI131624-01A1, 1 R21 NS108159-01 and 1 R21AI142186-01A1), the US National Multiple Sclerosis Society (1 RG1701-26628), the Weill Institute and the Maisin Foundation.

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Glossary

B cell receptor

(BCR). A cell-surface immunoglobulin composed of two paired heavy (H) and light (L) chains. Each chain is generated by irreversible rearrangement and recombination of the B cell variable (V), diversity (D; heavy chain only) and junction (J) genes.

Germinal centre reaction

The formation of secondary lymphoid tissue, which is the site of B cell somatic hypermutation and isotype switching.

Immunoglobulin class switching

Also called ‘isotype class switching’ or ’class-switch recombination’, this process refers to recombination of the immunoglobulin gene constant (C) region to allow generation of IgG, IgA or IgE isotypes.

Antibody isotypes

Antibodies are of five different isotypes: IgM, IgD, IgG, IgA and IgE. IgM and IgD are co-expressed by naive B cells, whereas the other isotypes are expressed by antigen-experienced B cells. Isotype is determined by the constant (C) region of the immunoglobulin gene, which encodes the antibody Fc region and binds to Fc receptors on various immune effector cell types.

Somatic hypermutation

Insertion of point mutations into the immunoglobulin gene variable (V) region, which increases antibody diversity and allows the generation of antibodies with high affinity for antigen (affinity maturation).

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Sabatino, J.J., Pröbstel, AK. & Zamvil, S.S. B cells in autoimmune and neurodegenerative central nervous system diseases. Nat Rev Neurosci 20, 728–745 (2019). https://doi.org/10.1038/s41583-019-0233-2

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