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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0309203

Received for publication March 26, 2009.
Revised May 18, 2009.
Accepted for publication May 26, 2009.

Article

Hyperactivated B cells in human inflammatory bowel disease

Ansu Mammen Noronha *{dagger}, YanMei Liang *, Jeremy T. Hetzel *{dagger}, Hatice Hasturk {ddagger}, Alpdogan Kantarci {ddagger}, Arthur Stucchi {sect}, Yue Zhang ||, Barbara S. Nikolajczyk ||, Francis A. Farraye {dagger}, and Lisa M. Ganley-Leal *@

*Section of Infectious Disease, Department of Medicine, and{dagger}Section of Gastroenterology, Boston Medical Center, Departments{sect}Surgery, Pathology and Laboratory Medicine, ||Microbiology, Boston University School of Medicine, and{ddagger}Department of Periodontology and Oral Biology, Boston University, Goldman School of Dental Medicine, Boston, Massachusetts, USA

@ To whom correspondence should be addressed. E-mail: lisa.ganleyleal{at}bmc.org.


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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.

Key Words: inflammation • Toll-like receptor 2 • IL-8 • Crohn’s disease • ulcerative colitis