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Circulating CD40+ and CD86+ B cell subsets demonstrate opposing associations with risk of stroke
Polyxeni T Mantani1, Irena Ljungcrantz, Linda Andersson
1From the Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden (P.T.M., I.L., L.A., R.A., B.H., H.B., J.N., G.N.F.); and Faculty of Health and Society, Malmö University, Malmö, Sweden (G.N.F.).
Objective:
Accumulating evidence shows that immune cells play an important role in atherosclerosis. Most attention has focused on the role of different T cell subsets, whereas the possible involvement of B cells has been less studied. In this study, we assessed the association of 2 different B cell subsets, CD19(+)CD40(+) and CD19(+)CD86(+) B cells, with risk for development of acute cardiovascular events.
Approach And Results:
The prospective study included 700 subjects randomly selected from the cardiovascular cohort of the Malmö Diet and Cancer study. Mononuclear leukocytes, stored at -140(○)C at the baseline investigation in 1991-1994, were thawed and B cell subsets analyzed by flow cytometry. Cytokine release from CD3/CD28-stimulated mononuclear leukocytes was measured with multiplex ELISA. Baseline carotid intima-media thickness and stenosis were assessed by ultrasonography, and clinical events were monitored through validated national registers during a median/mean follow-up time of 15 years. The subjects in the highest tertile of CD19(+)CD40(+) B cells had a significantly lower risk of incident stroke after adjustment for other risk factors. In contrast, CD19(+)CD86(+) B cells were associated with higher risk for development of a stroke event and increased release of proinflammatory cytokines from mononuclear leukocytes.
Conclusions:
These observations provide evidence for an involvement of B cells in the incidence of stroke and suggest that both pathogenic and protective B cell subsets exist.
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