Pathogenic role of B cells in anti-CD40-induced necroinflammatory liver disease

The American Journal of Pathology
Kiminori KimuraFrancis V Chisari

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.

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Citations

Apr 10, 2008·The Journal of Clinical Investigation·Juliana HamzahRuth Ganss
Oct 18, 2012·Brain, Behavior, and Immunity·Heidemarie GastAdriano Fontana
Aug 30, 2008·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Kiminori KimuraKazuhiro Kakimi
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Apr 9, 2008·Journal of Hepatology·Kiminori KimuraHisataka Moriwaki
Feb 11, 2015·Experimental and Therapeutic Medicine·Hong-Hui ShenPan-Yong Mao
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Nov 26, 2010·Journal of Leukocyte Biology·Kiminori KimuraMichinori Kohara
Sep 30, 2018·Gastroenterology·Barbara Rehermann, Robert Thimme

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