title: Depletion of B cells induces remission of autoimmune hepatitis in mice through reduced antigen presentation and help to T cells.
abstract: Autoimmune hepatitis (AIH) is known as a T cell-mediated disease. However, AIH patients refractory to conventional treatment have been successfully treated with anti-CD20-mediated B-cell depletion. The aim of this project was to understand the immunological changes underlying the AIH remission caused by B-cell depletion in an experimental model of AIH. C57BL/6 AIH mice, xenoimmunized with DNA coding for human liver antigens, were treated with a single dose of depleting mouse anti-CD20 antibody at the peak of liver inflammation. Liver inflammation, alanine aminotransferase levels, chemokine (C-X-C) ligand 10 expression, and circulating B-cell, autoantibody, and total immunoglobulin G levels were monitored following depletion. T-cell and B-cell phenotype and function were characterized. Administration of a single dose of anti-CD20 resulted in a drastic reduction of liver inflammation accompanied by a significant reduction of alanine aminotransferase levels and of proinflammatory chemokine (C-X-C) ligand 10 expression. The treatment did not result in significant changes in total immunoglobulin G levels or autoantibodies. There were significantly more naive and less antigen-experienced CD4+ and CD8+ T cells, and T-cell proliferation was significantly reduced following anti-CD20 treatment. B cells served as antigen-presenting cells to CD4+ T cells. Anti-CD20 treatment also led to a profound reduction of T follicular helper cells.
  
  
  CONCLUSIONS
  B cells play an active role in the pathogenesis of AIH in antigen presentation processes and the modulation of T-cell functions and influence the T follicular helper-cell population; this active role of B cells could explain the success of B-cell depletion for remission of AIH despite its classification as a T cell-mediated autoimmune liver disease.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, CHU Sainte-Justine, Montreal, QC, Canada.
authors.forename: Kathie
authors.initials: K
authors.lastname: Béland
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, CHU Sainte-Justine, Montreal, QC, Canada.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Marceau
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, CHU Sainte-Justine, Montreal, QC, Canada.
authors.forename: Agathe
authors.initials: A
authors.lastname: Labardy
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, CHU Sainte-Justine, Montreal, QC, Canada.
authors.forename: Sara
authors.initials: S
authors.lastname: Bourbonnais
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, CHU Sainte-Justine, Montreal, QC, Canada.|Microbiology and Immunology Department.|Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Alvarez
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D018951:Antigens, CD20 / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D019693:Hepatitis, Autoimmune / Q000276:immunology*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018951:Antigens, CD20; D001324:Autoantigens; D016207:Cytokines