A Novel Hypothesis: Regulatory B Lymphocytes Shape Outcome from Experimental Stroke

Halina Offner, Patricia D. Hurn

Research output: Contribution to journalArticle

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)324-330
Number of pages7
JournalTranslational Stroke Research
Volume3
Issue number3
DOIs
StatePublished - Sep 1 2012

Keywords

  • Bregs
  • Experimental stroke
  • IL-10
  • Immunotherapy
  • PD-1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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