Journal
ACTA NEUROPATHOLOGICA
Volume 145, Issue 4, Pages 461-477Publisher
SPRINGER
DOI: 10.1007/s00401-023-02552-6
Keywords
Regulatory B cells; Interleukin-10; Multiple sclerosis; Experimental autoimmune encephalomyelitis; Myeloid cells; Microglia
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B cells contribute to chronic inflammatory conditions, but removal of B cells may enhance the activity of monocytes. B cell-provided interleukin-10 (IL-10) plays a key role in controlling the pro-inflammatory activity of peripheral myeloid cells and microglia. Depleting B cells in a mouse model of multiple sclerosis (MS) accelerates disease severity, while adoptive transfer of IL-10-providing B cells reverses clinical exacerbation.
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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