title: A novel hypothesis: regulatory B lymphocytes shape outcome from experimental stroke.
abstract: Although inflammatory immune cells clearly contribute to the development of middle cerebral artery occlusion (MCAO) in mice, the failure to block neutrophil-associated injury in clinical stroke trials has discouraged further development of immunotherapeutic approaches. However, there is renewed interest in a possible protective role for regulatory T- and B-cells that can suppress inflammation and limit central nervous system damage induced by infiltrating pro-inflammatory cells. Our failure to implicate CD4(+)FoxP3(+) T-cells in limiting brain lesion volume after MCAO turned our focus towards regulatory B-cells known to mediate protection against other inflammatory CNS conditions. Our results clearly demonstrated that B-cell deficient mice developed larger infarct volumes, higher mortality and more severe functional deficits compared to wild-type mice, and had increased numbers of activated T-cells, macrophages, microglial cells, and neutrophils in the affected brain hemisphere. These MCAO-induced changes were completely prevented in B-cell-restored mice after transfer of highly purified WT B-cells but not IL-10-deficient B-cells. 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: Neuroimmunology Research, Portland VA Medical Center, R&D-31, 3710 SW US Veterans Hospital Rd., Portland, OR 97239 ; Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201 ; Department of Anesthesiology and Peri-Operative Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239.
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
authors.forename: Patricia D
authors.initials: PD
authors.lastname: Hurn