Background & Aims: Mice that express a dominant-negative form of transforming growth factor-β receptor restricted to T cells (dnTGF-βRII) 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 (Igμ-/-) with dnTGF-βRII mice, creating Igμ-/-dnTGF-βRII mice, and compared the resulting disease phenotype with that of dnTGF-βRII mice (controls). We also performed adoptive transfer of dnTGF-βRII 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 Igμ-/-dnTGF-βRII mice unexpectedly developed a more severe form of cholangitis than controls (dnTGF-βRII 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 Igμ-/-dnTGF-βRII mice had increased levels of proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) and developed a more severe form of colitis than controls. Adoptive transfer of CD8+ splenocytes from dnTGF-βRII 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. Conclusion: B cells have a suppressive effect on the inflammatory response in the dnTGF-βRII model of primary biliary cirrhosis.
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