title: Pathogenic role of B cells in anti-CD40-induced necroinflammatory liver disease.
abstract: Activated B cells function in antibody production and antigen presentation, but whether they perform any pathophysiological functions at sites of inflammation is not fully understood. Here, we report that intravenous injection of an agonistic anti-CD40 monoclonal antibody (alphaCD40) causes a biphasic inflammatory liver disease in inbred mice. The late phase of disease was suppressed in B-cell-deficient mice and by the depletion of macrophages, but not T cells or natural killer cells. We also report that SCID mice were not susceptible to alphaCD40-induced liver disease unless they were reconstituted with normal B cells and that B cells as well as macrophages played key roles in alphaCD40-induced late phase of liver inflammation. Finally, liver disease and the recruitment of inflammatory cells into the liver were mediated by interferon-gamma and tumor necrosis factor-alpha, but not by Fas. In conclusion, these results indicate that CD40 ligation can trigger a B-cell-mediated inflammatory response that can have pathogenic consequences for the liver.
authors.affiliation: First Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan. kkimura@cc.gifu-u.ac.jp
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kimura
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
authors.forename: Masahito
authors.initials: M
authors.lastname: Nagaki
authors.forename: Masanao
authors.initials: M
authors.lastname: Saio
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Nakamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Naito
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kuwata
authors.forename: Francis V
authors.initials: FV
authors.lastname: Chisari
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019013:CD40 Antigens / Q000187:drug effects / Q000276:immunology*; D006505:Hepatitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D009336:Necrosis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma