title: Role of intrahepatic B cells in non-alcoholic fatty liver disease by secreting pro-inflammatory cytokines and regulating intrahepatic T cells.
abstract: OBJECTIVE
  To investigate the alterations and functions of intrahepatic B (IHB) cells in non-alcoholic fatty liver disease (NAFLD) model induced by high-fat diet (HFD).
  
  
  METHODS
  C57BL/6 J mice were fed with HFD for 16 weeks to induce NAFLD. Flow cytometry was used to analyze lymphocytes from liver, spleen and peripheral blood mononuclear cells (PBMC). Real-time polymerase chain reaction and immunofluorescence stain were applied to investigate cytokine expression in the intrahepatic lymphocytes and IHB cells. CD4(+) intrahepatic T (IHT) cells and IHB cells were enriched by a magnetic-activated cell sorting method and cultured in vitro. The cytokines and immunoglobulin (Ig) levels in the plasma, cultural supernatants and liver homogenates were monitored with cytometric bead arrays or multiplex immunoassays.
  
  
  RESULTS
  The percentage of IHB cells in CD45(+) cells was significantly higher in the NAFLD group than in the control group (P < 0.05). IHB cells expressed higher levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the NAFLD group, and produced higher levels of IL-6 and TNF-α under the stimulation of lipopolysaccharide (LPS) than the control group. IgG2a levels were higher in the plasma, liver homogenates and the culture supernatants of IHB cells after stimulated by LPS and anti-CD40/IgM in the NAFLD group than in the control group. Moreover, IHB cells enhanced the activation of CD4(+) IHT cells and promoted the differentiation into T helper (Th) 1 cells in the NAFLD group.
  
  
  CONCLUSIONS
  IHB cells might be involved in NAFLD both by inducing the secretion of IL-6, TNF-α and IgG2a and by enhancing the activation of CD4(+) IHT cells and their differentiation into Th1 cells.
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
authors.forename: Wei Wei
authors.initials: WW
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
authors.forename: Xin Yun
authors.initials: XY
authors.lastname: Qiu
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Institute of Clinical Molecular Biology, Peking University People's Hospital, Beijing, China.
authors.forename: Yu Jing
authors.initials: YJ
authors.lastname: Chi
authors.affiliation: Peking University Hepatology Institute, Peking University People's Hospital, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Cong
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing, China. liuyulan@pkuph.edu.cn.
authors.forename: Yu Lan
authors.initials: YL
authors.lastname: Liu
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D059305:Diet, High-Fat; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D018836:Inflammation Mediators / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides; D008099:Liver / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D008070:Lipopolysaccharides
keywords: B-lymphocytes; T-lymphocytes; cytokines; immunoglobulin G; non-alcoholic fatty liver disease