title: Regulatory B cells limit CNS inflammation and neurologic deficits in murine experimental stroke.
abstract: Evaluation of infarct volumes and infiltrating immune cell populations in mice after middle cerebral artery occlusion (MCAO) strongly implicates a mixture of both pathogenic and regulatory immune cell subsets in stroke pathogenesis and recovery. Our goal was to evaluate the contribution of B cells to the development of MCAO by comparing infarct volumes and functional outcomes in wild-type (WT) versus B-cell-deficient μMT(-/-) mice. The results clearly demonstrate larger infarct volumes, higher mortality, more severe functional deficits, and increased numbers of activated T cells, macrophages, microglial cells, and neutrophils in the affected brain hemisphere of MCAO-treated μMT(-/-) versus WT mice. These MCAO-induced changes were completely prevented in B-cell-restored μMT(-/-) mice after transfer of highly purified WT GFP(+) B cells that were detected in the periphery, but not the CNS. In contrast, transfer of B cells from IL-10(-/-) mice had no effect on infarct volume when transferred into μMT(-/-) mice. These findings strongly support a previously unrecognized activity of IL-10-secreting WT B cells to limit infarct volume, mortality rate, recruitment of inflammatory cells, and functional neurological deficits 48 h after MCAO. Our novel observations are the first to implicate IL-10-secreting B cells as a major regulatory cell type in stroke and suggest that enhancement of regulatory B cells might have application as a novel therapy for this devastating neurologic condition.
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, Oregon 97239, USA.
authors.forename: Xuefang
authors.initials: X
authors.lastname: Ren
authors.forename: Kozaburo
authors.initials: K
authors.lastname: Akiyoshi
authors.forename: Suzan
authors.initials: S
authors.lastname: Dziennis
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
authors.forename: Paco S
authors.initials: PS
authors.lastname: Herson
authors.forename: Patricia D
authors.initials: PD
authors.lastname: Hurn
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D004660:Encephalitis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D005434:Flow Cytometry; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016753:Interleukin-10 / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018709:Statistics, Nonparametric
chemical_list: D016753:Interleukin-10