Ectopic CD40 ligand expression on B cells triggers intestinal inflammation
Ectopic CD40 ligand expression on B cells triggers intestinal inflammation
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DOI：
10.4049/jimmunol.172.10.6388
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发表时间：
2004-05-15
影响因子：
4.4
通讯作者：
Watanabe, M
中科院分区：
文献类型：
--
作者：
Kawamura, T;Kanai, T;Watanabe, M
一些研究表明，在人类炎症性肠病的小鼠模型中，CD4(+)T细胞、巨噬细胞和树突状细胞最初介导了肠道炎症。然而，B细胞在肠道炎症发展中的最初作用仍不清楚。在这项研究中，我们通过异位表达CD40配体(CD40L)的转基因(TG)小鼠(CD40L/BTG)提供了B细胞可以引发肠道炎症的证据。我们证明CD40L/B转基因小鼠在8-15周龄时自发地在结肠和回肠出现严重的跨壁肠炎。相反，CD40L/B TgxCD40(-/-)双突变小鼠未发生结肠炎，提示CD40-CD40L相互作用直接参与肠道炎症的发生发展。炎症浸润物主要由大量聚集的、IgM阳性的B细胞组成。这些小鼠的特征还包括抗结肠自身抗体的存在和干扰素-γ的产生增加。此外，尽管单独转移CD40L/BTG小鼠的CD4(+)T细胞或同时转移CD4(+)T细胞和B220(+)B细胞，而不是单独转移来自CD40L/BTG小鼠的B220(+)细胞，小鼠也会发生结肠炎，但转移来自CD40L/BTG小鼠的B220(+)B细胞和来自野生型小鼠的CD4(+)T细胞也会发生结肠炎，这表明TG B细胞应该是该结肠炎模型的触发因素，而T细胞作为效应细胞参与其中。由于CD40L在某些自身免疫性疾病中异位表达于B细胞上，本研究提示B细胞可能在人类炎症性肠病的肠道炎症中起作用。
Several studies indicate that CD4(+) T cells, macrophages, and dendritic cells initially mediate intestinal inflammation in murine models of human inflammatory bowel disease. However, the initial role of B cells in the development of intestinal inflammation remains unclear. In this study we present evidence that B cells can trigger intestinal inflammation using transgenic (Tg) mice expressing CD40 ligand (CD40L) ectopically on B cells (CD40L/B Tg). We demonstrated that CD40L/B Tg mice spontaneously developed severe transmural intestinal inflammation in both colon and ileum at 8-15 wk of age. In contrast, CD40L/B TgxCD40(-/-) double-mutant mice did not develop colitis, indicating the direct involvement of CD40-CD40L interaction in the development of intestinal inflammation. The inflammatory infiltrates consisted predominantly of massive aggregated, IgM-positive B cells. These mice were also characterized by the presence of anti-colon autoantibodies and elevated IFN-gamma production. Furthermore, although mice transferred with CD4(+) T cells alone or with both CD4(+) T and B220(+) B cells, but not B220(+) cells alone, from diseased CD40L/B Tg mice, develop colitis, mice transferred with B220(+) B cells from diseased CD40L/B Tg mice and CD4(+) T cells from wild-type mice also develop colitis, indicating that the Tg B cells should be a trigger for this colitis model, whereas T cells are involved as effectors. As it has been demonstrated that CD40L is ectopically expressed on B cells in some autoimmune diseases, the present study suggests the possible contribution of B cells in triggering intestinal inflammation in human inflammatory bowel disease.