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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
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.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
ISSN:0002-9440
1525-2191
DOI:10.2353/ajpath.2006.050314