Hyperactivated B cells in human inflammatory bowel disease.
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.
Noronha
Ansu Mammen
AM
Section of Infectious Disease, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Liang
YanMei
Y
Hetzel
Jeremy T
JT
Hasturk
Hatice
H
Kantarci
Alpdogan
A
Stucchi
Arthur
A
Zhang
Yue
Y
Nikolajczyk
Barbara S
BS
Farraye
Francis A
FA
Ganley-Leal
Lisa M
LM
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*
C508606:CXCL8 protein, human; D016209:Interleukin-8; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2