title: Hyperactivated B cells in human inflammatory bowel disease.
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.
authors: Section of Infectious Disease, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors: Ansu Mammen
authors: AM
authors: Noronha
authors: YanMei
authors: Y
authors: Liang
authors: Jeremy T
authors: JT
authors: Hetzel
authors: Hatice
authors: H
authors: Hasturk
authors: Alpdogan
authors: A
authors: Kantarci
authors: Arthur
authors: A
authors: Stucchi
authors: Yue
authors: Y
authors: Zhang
authors: Barbara S
authors: BS
authors: Nikolajczyk
authors: Francis A
authors: FA
authors: Farraye
authors: Lisa M
authors: LM
authors: Ganley-Leal
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000276:immunology*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2