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B\u00a0cells or B\u00a0cell 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\u00a0cells contain regulatory features and that their removal enhanced activity of monocytes. Using a co-culture system, we identified B\u00a0cell-provided interleukin (IL)-10 as key factor in controlling pro-inflammatory activity of peripheral myeloid cells as well as microglia. Depleting B\u00a0cells 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\u00a0cells restored in vivo control of central nervous system (CNS) macrophages and microglia and reversed clinical exacerbation. These findings suggest that B\u00a0cells exert meaningful regulatory properties, which should be considered when designing novel B\u00a0cell-directed agents.<\/jats:p>","DOI":"10.1007\/s00401-023-02552-6","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T03:02:40Z","timestamp":1677639760000},"page":"461-477","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["IL-10-providing B\u00a0cells govern pro-inflammatory activity of macrophages and microglia in CNS autoimmunity"],"prefix":"10.1007","volume":"145","author":[{"given":"Anastasia","family":"Geladaris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"H\u00e4usser-Kinzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxanne","family":"Pretzsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitzan","family":"Nissimov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Lehmann-Horn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darius","family":"H\u00e4usler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8409-0389","authenticated-orcid":false,"given":"Martin S.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,1]]},"reference":[{"key":"2552_CR1","doi-asserted-by":"publisher","unstructured":"Bar-Or A, Grove RA, Austin DJ, Tolson JM, VanMeter SA, Lewis EW, Derosier FJ, Lopez MC, Kavanagh ST, Miller AE et al (2018) Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis. 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