title: B cells suppress the inflammatory response in a mouse model of primary biliary cirrhosis.
abstract: OBJECTIVE
  Mice that express a dominant-negative form of transforming growth factor-beta receptor restricted to T cells (dnTGF-betaRII) develop antimitochondrial antibodies and liver inflammation similar to human primary biliary cirrhosis.
  
  
  METHODS
  To address the role of B cells in this model of primary biliary cirrhosis, we bred B cell-deficient mice (Igmu(-/-)) with dnTGF-betaRII mice, creating Igmu(-/-)dnTGF-betaRII mice, and compared the resulting disease phenotype with that of dnTGF-betaRII mice (controls). We also performed adoptive transfer of dnTGF-betaRII CD8(+) splenocytes, with or without B cells, to 8-week-old female Rag-1(-/-) mice to assess the role of B cells in the inflammatory response.
  
  
  RESULTS
  The B cell-deficient Igmu(-/-)dnTGF-betaRII mice unexpectedly developed a more severe form of cholangitis than controls (dnTGF-betaRII mice) and had a significantly greater frequency of activated CD4(+) and CD8(+) T cells in the liver. They also had reduced frequency of Foxp3(+) regulatory T cells in the hepatic CD4(+) T-cell population and natural killer (NK) T cells (NK1.1(+) CD3(+)) in hepatic inflammatory cell infiltrates. The Igmu(-/-)dnTGF-betaRII mice had increased levels of proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) and developed a more severe form of colitis than controls. Adoptive transfer of CD8(+) splenocytes from dnTGF-betaRII mice and peritoneal cavity-derived, but not spleen-derived, CD19(+) B cells into Rag-1(-/-) mice resulted in decreased amounts of liver inflammation and bile duct damage, compared with Rag-1(-/-) mice in which only CD8(+) splenocytes were transferred.
  
  
  CONCLUSIONS
  B cells have a suppressive effect on the inflammatory response in the dnTGF-betaRII model of primary biliary cirrhosis.
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, California, USA.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Moritoki
authors.forename: Weici
authors.initials: W
authors.lastname: Zhang
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yoshida
authors.forename: Kanji
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: Guo-Xiang
authors.initials: GX
authors.lastname: Yang
authors.forename: Christopher
authors.initials: C
authors.lastname: Bowlus
authors.forename: William M
authors.initials: WM
authors.lastname: Ridgway
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.forename: Ross L
authors.initials: RL
authors.lastname: Coppel
authors.forename: Ian R
authors.initials: IR
authors.lastname: Mackay
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.forename: Zhe-Xiong
authors.initials: ZX
authors.lastname: Lian
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D004195:Disease Models, Animal; D007108:Immune Tolerance / Q000276:immunology*; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D018125:Receptors, Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II