Pathogenic role of B cells in anti-CD40-induced necroinflammatory liver disease
Pathogenic role of B cells in anti-CD40-induced necroinflammatory liver disease
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DOI：
10.2353/ajpath.2006.050314
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发表时间：
2006-03-01
影响因子：
6
通讯作者：
Chisari, FV
中科院分区：
文献类型：
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作者：
Kimura, K;Moriwaki, H;Chisari, FV
活化的B细胞在抗体产生和抗原提呈中发挥作用，但它们是否在炎症部位发挥任何病理生理功能尚不完全清楚。在这里，我们报告静脉注射激动型抗CD40单抗(αCD40)在近交系小鼠中引起双相炎症性肝病。在B细胞缺陷的小鼠中，疾病的晚期被抑制，并通过耗尽巨噬细胞，但不是T细胞或自然杀伤细胞。我们还报道，SCID小鼠除非用正常的B细胞重建，否则不容易感染αCD40诱导的肝脏疾病，并且B细胞和巨噬细胞在αCD40诱导的肝脏炎症的晚期起关键作用。最后，肝脏疾病和炎症细胞重新进入肝脏是由干扰素-γ和肿瘤坏死因子-α介导的，而不是由Fas介导的。总之，这些结果表明，CD40结扎可以触发B细胞介导的炎症反应，这可能会对肝脏产生致病后果。
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 (alpha CD40) 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 alpha CD40-induced liver disease unless they were reconstituted with normal B cells and that B cells as well as macrophages played key roles in alpha CD40-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.