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 |
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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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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.</description><identifier>ISSN: 0002-9440</identifier><identifier>EISSN: 1525-2191</identifier><identifier>DOI: 10.2353/ajpath.2006.050314</identifier><identifier>PMID: 16507894</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>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</subject><ispartof>The American journal of pathology, 2006-03, Vol.168 (3), p.786-795</ispartof><rights>2006 American Society for Investigative Pathology</rights><rights>Copyright © American Society for Investigative Pathology 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c581t-8127dde53461a0183d2b8e016f13a7a8e3d8b06cbcc58768fa504f0deaa842223</citedby><cites>FETCH-LOGICAL-c581t-8127dde53461a0183d2b8e016f13a7a8e3d8b06cbcc58768fa504f0deaa842223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1606511/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0002944010621396$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,3537,27901,27902,53766,53768,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16507894$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kimura, Kiminori</creatorcontrib><creatorcontrib>Moriwaki, Hisataka</creatorcontrib><creatorcontrib>Nagaki, Masahito</creatorcontrib><creatorcontrib>Saio, Masanao</creatorcontrib><creatorcontrib>Nakamoto, Yasunari</creatorcontrib><creatorcontrib>Naito, Makoto</creatorcontrib><creatorcontrib>Kuwata, Kazuo</creatorcontrib><creatorcontrib>Chisari, Francis V.</creatorcontrib><title>Pathogenic Role of B Cells in Anti-CD40-Induced Necroinflammatory Liver Disease</title><title>The American journal of pathology</title><addtitle>Am J Pathol</addtitle><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.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>B-Lymphocytes - drug effects</subject><subject>B-Lymphocytes - immunology</subject><subject>CD40 Antigens - drug effects</subject><subject>CD40 Antigens - immunology</subject><subject>Hepatitis - immunology</subject><subject>Hepatitis - metabolism</subject><subject>Hepatitis - pathology</subject><subject>Interferon-gamma - metabolism</subject><subject>Liver - drug effects</subject><subject>Liver - immunology</subject><subject>Liver - pathology</subject><subject>Lymphocyte Activation</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Necrosis</subject><subject>Original Research Paper</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>0002-9440</issn><issn>1525-2191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkVFv0zAQxy3ExMrgC_CA8sRbyp2dOI6EkLaOjUkVQwieLde5tJ6SuNhp0b49rlKx7YU9WZZ_9_fd_Rh7hzDnohQfzd3WjJs5B5BzKEFg8YLNsORlzrHGl2wGADyviwJO2esY79JVCgWv2CnKEipVFzN2-z1F-DUNzmY_fEeZb7OLbEFdFzM3ZOfD6PLFZQH5zdDsLDXZN7LBu6HtTN-b0Yf7bOn2FLJLF8lEesNOWtNFens8z9ivqy8_F1_z5e31zeJ8mdtS4Zgr5FXTUCkKiQZQiYavFAHKFoWpjCLRqBVIu7KJr6RqTQlFCw0ZowrOuThjn6fc7W7VU2NpGIPp9Da43oR77Y3TT18Gt9Frv9coQZaIKeDDMSD43zuKo-5dtGluM5DfRS2rCkCI50GOArGuDyCfwLSgGAO1_7pB0AdhehKmD8L0JCwVvX88x0PJ0dDD9xu33vxxgXTsTdclHA95KJUWulIygZ8mkNLa946CjtbRkJylIjvqxrv_NfIXueyzrQ</recordid><startdate>20060301</startdate><enddate>20060301</enddate><creator>Kimura, Kiminori</creator><creator>Moriwaki, Hisataka</creator><creator>Nagaki, Masahito</creator><creator>Saio, Masanao</creator><creator>Nakamoto, Yasunari</creator><creator>Naito, Makoto</creator><creator>Kuwata, Kazuo</creator><creator>Chisari, Francis V.</creator><general>Elsevier Inc</general><general>ASIP</general><general>American Society for Investigative Pathology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20060301</creationdate><title>Pathogenic Role of B Cells in Anti-CD40-Induced Necroinflammatory Liver Disease</title><author>Kimura, Kiminori ; 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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. 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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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