Hyperactivated B cells in human inflammatory bowel disease

Ansu Mammen Noronha, Yanmei Liang, Jeremy T. Hetzel, Hatice Hasturk, Alpdogan Kantarci, Arthur Stucchi, Yue Zhang, Barbara S. Nikolajczyk, Francis A. Farraye, Lisa M. Ganley-Leal

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

IBD is characterized by a chronic, dysregulated immune response to intestinal bacteria. Past work has focused on the role of T cells and myeloid cells in mediating chronic gastrointestinal and systemic inflammation. Here, we show that circulating and tissue B cells from CD patients demonstrate elevated basal levels of activation. CD patient B cells express surface TLR2, spontaneously secrete high levels of IL-8, and contain increased ex vivo levels of phosphorylated signaling proteins. CD clinical activity correlates directly with B cell expression of IL-8 and TLR2, suggesting a positive relationship between these B cell inflammatory mediators and disease pathogenesis. In contrast, B cells from UC patients express TLR2 but generally do not demonstrate spontaneous IL-8 secretion; however, significant IL-8 production is inducible via TLR2 stimulation. Furthermore, UC clinical activity correlates inversely with levels of circulating TLR2+ B cells, which is opposite to the association observed in CD. In conclusion, TLR2+ B cells are associated with clinical measures of disease activity and differentially associated with CD- and UC-specific patterns of inflammatory mediators, suggesting a formerly unappreciated role of B cells in the pathogenesis of IBD.

Original languageEnglish
Pages (from-to)1007-1016
Number of pages10
JournalJournal of Leukocyte Biology
Volume86
Issue number4
DOIs
StatePublished - Oct 2009

Keywords

  • Crohn's disease
  • IL-8
  • Inflammation
  • Toll-like receptor 2
  • Ulcerative colitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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