Circulating CD40+ and CD86+ B cell subsets demonstrate opposing associations with risk of stroke

Arterioscler Thromb Vasc Biol. 2014 Jan;34(1):211-8. doi: 10.1161/ATVBAHA.113.302667. Epub 2013 Nov 7.

Abstract

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.

Keywords: B-lymphocyte subsets; carotid artery diseases; prospective studies; stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD19 / blood
  • B-Lymphocyte Subsets / immunology*
  • B7-2 Antigen / blood*
  • Biomarkers / blood
  • CD40 Antigens / blood*
  • Carotid Intima-Media Thickness
  • Carotid Stenosis / blood
  • Carotid Stenosis / diagnosis
  • Carotid Stenosis / epidemiology
  • Carotid Stenosis / immunology*
  • Cells, Cultured
  • Chi-Square Distribution
  • Cytokines / metabolism
  • Disease-Free Survival
  • Female
  • Humans
  • Incidence
  • Inflammation Mediators / metabolism
  • Kaplan-Meier Estimate
  • Linear Models
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Stroke / blood
  • Stroke / diagnosis
  • Stroke / epidemiology
  • Stroke / immunology*
  • Sweden / epidemiology
  • Time Factors

Substances

  • Antigens, CD19
  • B7-2 Antigen
  • Biomarkers
  • CD40 Antigens
  • CD86 protein, human
  • Cytokines
  • Inflammation Mediators