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

Research output: Contribution to journalArticle

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
Publication statusPublished - 2004 May 15
Externally publishedYes

Fingerprint

CD40 Ligand
B-Lymphocytes
Inflammation
Colitis
Transgenic Mice
T-Lymphocytes
Inflammatory Bowel Diseases
Colon
Ileum
Autoantibodies
Dendritic Cells
Autoimmune Diseases
Immunoglobulin M
Macrophages

ASJC Scopus subject areas

  • Immunology

Cite this

Kawamura, T., Kanai, T., Dohi, T., Uraushihara, K., Totsuka, T., Iiyama, R., ... Watanabe, M. (2004). Ectopic CD40 Ligand Expression on B Cells Triggers Intestinal Inflammation. Journal of Immunology, 172(10), 6388-6397.

Ectopic CD40 Ligand Expression on B Cells Triggers Intestinal Inflammation. / Kawamura, Takahiro; Kanai, Takanori; Dohi, Taeko; Uraushihara, Koji; Totsuka, Teruji; Iiyama, Ryoichi; Taneda, Chikara; Yamazaki, Motomi; Nakamura, Tetsuya; Higuchi, Tetsuya; Aiba, Yuichi; Tsubata, Takeshi; Watanabe, Mamoru.

In: Journal of Immunology, Vol. 172, No. 10, 15.05.2004, p. 6388-6397.

Research output: Contribution to journalArticle

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, vol. 172, no. 10, pp. 6388-6397.
Kawamura T, Kanai T, Dohi T, Uraushihara K, Totsuka T, Iiyama R et al. Ectopic CD40 Ligand Expression on B Cells Triggers Intestinal Inflammation. Journal of Immunology. 2004 May 15;172(10):6388-6397.
Kawamura, Takahiro ; Kanai, Takanori ; Dohi, Taeko ; Uraushihara, Koji ; Totsuka, Teruji ; Iiyama, Ryoichi ; Taneda, Chikara ; Yamazaki, Motomi ; Nakamura, Tetsuya ; Higuchi, Tetsuya ; Aiba, Yuichi ; Tsubata, Takeshi ; Watanabe, Mamoru. / Ectopic CD40 Ligand Expression on B Cells Triggers Intestinal Inflammation. In: Journal of Immunology. 2004 ; Vol. 172, No. 10. pp. 6388-6397.
@article{45da370e66084cf8add135e7f71d06af,
title = "Ectopic CD40 Ligand Expression on B Cells Triggers Intestinal Inflammation",
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.",
author = "Takahiro Kawamura and Takanori Kanai and Taeko Dohi and Koji Uraushihara and Teruji Totsuka and Ryoichi Iiyama and Chikara Taneda and Motomi Yamazaki and Tetsuya Nakamura and Tetsuya Higuchi and Yuichi Aiba and Takeshi Tsubata and Mamoru Watanabe",
year = "2004",
month = "5",
day = "15",
language = "English",
volume = "172",
pages = "6388--6397",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - Ectopic CD40 Ligand Expression on B Cells Triggers Intestinal Inflammation

AU - Kawamura, Takahiro

AU - Kanai, Takanori

AU - Dohi, Taeko

AU - Uraushihara, Koji

AU - Totsuka, Teruji

AU - Iiyama, Ryoichi

AU - Taneda, Chikara

AU - Yamazaki, Motomi

AU - Nakamura, Tetsuya

AU - Higuchi, Tetsuya

AU - Aiba, Yuichi

AU - Tsubata, Takeshi

AU - Watanabe, Mamoru

PY - 2004/5/15

Y1 - 2004/5/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=2442420974&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2442420974&partnerID=8YFLogxK

M3 - Article

C2 - 15128830

AN - SCOPUS:2442420974

VL - 172

SP - 6388

EP - 6397

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -