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Originally published online as doi:10.1189/jlb.0309203 on July 9, 2009

Published online before print July 9, 2009
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(Journal of Leukocyte Biology. 2009;86:1007-1016.)
© 2009 Society for Leukocyte Biology

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§, Yue Zhang||, Barbara S. Nikolajczyk||, Francis A. Farraye{dagger} and Lisa M. Ganley-Leal*,1

* Section of Infectious Disease, Department of Medicine, and
{dagger} Section of Gastroenterology, Boston Medical Center, Departments
§ 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

1. Correspondence: Section of Infectious Diseases, Boston University School of Medicine, 650 Albany Street, Room 630, Boston, MA 02118, USA. E-mail: lisa.ganleyleal{at}bmc.org

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