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Open Access 01-03-2023 | Multiple Sclerosis | Original Paper

IL-10-providing B cells govern pro-inflammatory activity of macrophages and microglia in CNS autoimmunity

Authors: Anastasia Geladaris, Silke Häusser-Kinzel, Roxanne Pretzsch, Nitzan Nissimov, Klaus Lehmann-Horn, Darius Häusler, Martin S. Weber

Published in: Acta Neuropathologica | Issue 4/2023

Abstract

B cells contribute to chronic inflammatory conditions as source of antibody-secreting plasma cells and as antigen-presenting cells activating T cells, making anti-CD20-mediated B cell depletion a widely used therapeutic option. B cells or B cell subsets may, however, exert regulatory effects, while to date, the immunological and/or clinical impact of these observations remained unclear. We found that in multiple sclerosis (MS) patients, B cells contain regulatory features and that their removal enhanced activity of monocytes. Using a co-culture system, we identified B cell-provided interleukin (IL)-10 as key factor in controlling pro-inflammatory activity of peripheral myeloid cells as well as microglia. Depleting B cells via anti-CD20 in a mouse model of MS unleashed the activity of myeloid cells and microglia and accelerated disease severity; in contrast, adoptive transfer of IL-10-providing B cells restored in vivo control of central nervous system (CNS) macrophages and microglia and reversed clinical exacerbation. These findings suggest that B cells exert meaningful regulatory properties, which should be considered when designing novel B cell-directed agents.

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Title: IL-10-providing B cells govern pro-inflammatory activity of macrophages and microglia in CNS autoimmunity
Authors: Anastasia Geladaris
Silke Häusser-Kinzel
Roxanne Pretzsch
Nitzan Nissimov
Klaus Lehmann-Horn
Darius Häusler
Martin S. Weber
Publication date: 01-03-2023
Publisher: Springer Berlin Heidelberg
Keyword: Multiple Sclerosis
Published in: Acta Neuropathologica / Issue 4/2023
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-023-02552-6

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IL-10-providing B cells govern pro-inflammatory activity of macrophages and microglia in CNS autoimmunity

Abstract

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Abstract

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