Pathogenic Role of B Cells in Anti-CD40-Induced Necroinflammatory Liver Disease

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 (αCD40) causes a biphasic i...

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Veröffentlicht in:The American journal of pathology 2006-03, Vol.168 (3), p.786-795
Hauptverfasser: Kimura, Kiminori, Moriwaki, Hisataka, Nagaki, Masahito, Saio, Masanao, Nakamoto, Yasunari, Naito, Makoto, Kuwata, Kazuo, Chisari, Francis V.
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container_issue 3
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container_title The American journal of pathology
container_volume 168
creator Kimura, Kiminori
Moriwaki, Hisataka
Nagaki, Masahito
Saio, Masanao
Nakamoto, Yasunari
Naito, Makoto
Kuwata, Kazuo
Chisari, Francis V.
description 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 (αCD40) 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 αCD40-induced liver disease unless they were reconstituted with normal B cells and that B cells as well as macrophages played key roles in αCD40-induced late phase of liver inflammation. Finally, liver disease and the recruitment of inflammatory cells into the liver were mediated by interferon-γ and tumor necrosis factor-α, 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.
doi_str_mv 10.2353/ajpath.2006.050314
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subjects Animals
Antibodies, Monoclonal - pharmacology
B-Lymphocytes - drug effects
B-Lymphocytes - immunology
CD40 Antigens - drug effects
CD40 Antigens - immunology
Hepatitis - immunology
Hepatitis - metabolism
Hepatitis - pathology
Interferon-gamma - metabolism
Liver - drug effects
Liver - immunology
Liver - pathology
Lymphocyte Activation
Mice
Mice, SCID
Necrosis
Original Research Paper
Tumor Necrosis Factor-alpha - metabolism
title Pathogenic Role of B Cells in Anti-CD40-Induced Necroinflammatory Liver Disease
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