title: T-bet-Expressing B Cells Are Positively Associated with Crohn's Disease Activity and Support Th1 Inflammation.
abstract: Pathogenesis of Crohn's disease (CD) is thought to involve the chronic activation of T helper 1 (Th1)- and Th17-mediated inflammation, such as the production of interferon-gamma (IFN-γ) and interleukin 17 (IL-17). However, studies have also shown that although IFN-γ is required, IFN-γ-producing or T-bet-expressing Th1 cells are dispensable. We therefore examined T-bet-expressing B cells as another source of IFN-γ that potentially supported intestinal inflammation in CD patients. We found that the frequencies of T-bet-expressing B cells were significantly upregulated and abundantly present in the gut of active, but not quiescent, CD patients. The frequencies of T-bet-expressing B cells were also directly correlated with CD disease activity. These T-bet+B cells were almost exclusively IgG expressing and produced significantly higher amounts of IFN-γ, IL-6, and IL-12 than IgA- and IgM-expressing T-bet-B cells. These B cells also supported IFN-γ production of CD4+T cells. T-bet expression was induced in vitro in peripheral blood B cells through the stimulation of B-cell receptor (BCR), Toll-like receptor 7 (TLR7), and IFN-γ, which resembled gut T-bet+B cells in terms of elevated IFN-γ. We found that these stimulated B cells, but not unstimulated B cells, supported the IFN-γ and IL-12 production from autologous CD4+T cells. In addition, in patients with higher gut T-bet+B-cell percentage, a higher frequency of gut-infiltrating IFN-γ+and IL-12+T cells was also observed. Together, our results suggested that T-bet-expressing B cells could contribute to the intestinal Th1 inflammation in CD patients.
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University , Nanjing, China .
authors.forename: Zhenlong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University , Nanjing, China .
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University , Nanjing, China .
authors.forename: Jinjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University , Nanjing, China .
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Diao
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University , Nanjing, China .
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Qian
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University , Nanjing, China .
authors.forename: Nan
authors.initials: N
authors.lastname: Zhu
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology* / Q000473:pathology*; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008297:Male; D020825:T-Box Domain Proteins / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor
keywords: B cell; Crohn's disease; T helper 1 cell