Ectopic CD40 Ligand Expression on B Cells Triggers Intestinal Inflammation

Takahiro Kawamura, Takanori Kanai, Taeko Dohi, Koji Uraushihara, Teruji Totsuka, Ryoichi Iiyama, Chikara Taneda, Motomi Yamazaki, Tetsuya Nakamura, Tetsuya Higuchi, Yuichi Aiba, Takeshi Tsubata, Mamoru Watanabe

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28 Citations (Scopus)

Abstract

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-γ 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.

Original languageEnglish
Pages (from-to)6388-6397
Number of pages10
JournalJournal of Immunology
Volume172
Issue number10
DOIs
Publication statusPublished - 2004 May 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kawamura, T., Kanai, T., Dohi, T., Uraushihara, K., Totsuka, T., Iiyama, R., Taneda, C., Yamazaki, M., Nakamura, T., Higuchi, T., Aiba, Y., Tsubata, T., & Watanabe, M. (2004). Ectopic CD40 Ligand Expression on B Cells Triggers Intestinal Inflammation. Journal of Immunology, 172(10), 6388-6397. https://doi.org/10.4049/jimmunol.172.10.6388