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Ectopic CD40 ligand expression on B cells triggers intestinal inflammation
Takahiro Kawamura1, Takanori Kanai, Taeko Dohi
1Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Journal of Immunology (Baltimore, Md. : 1950)
|May 7, 2004
Summary
B cells can trigger intestinal inflammation by expressing CD40 ligand (CD40L). This study shows that B cells, not T cells, initiate inflammation in a new mouse model of inflammatory bowel disease.
Area of Science:
- Immunology
- Gastroenterology
- Autoimmunity
Background:
- Intestinal inflammation in inflammatory bowel disease (IBD) is primarily mediated by CD4(+) T cells, macrophages, and dendritic cells.
- The specific role of B cells in initiating intestinal inflammation is not fully understood.
Purpose of the Study:
- To investigate the potential of B cells to trigger intestinal inflammation.
- To elucidate the mechanism by which B cells contribute to the development of IBD.
Main Methods:
- Generation of transgenic (Tg) mice (CD40L/B Tg) with ectopic CD40 ligand (CD40L) expression on B cells.
- Crossbreeding CD40L/B Tg mice with CD40-deficient mice (CD40(-/-)) to create double-mutant mice.
- Cell transfer experiments using T cells and B cells from diseased Tg mice.
Main Results:
- CD40L/B Tg mice spontaneously developed severe transmural intestinal inflammation.
- Inflammation was dependent on CD40-CD40L interaction, as evidenced by the absence of colitis in CD40L/B TgxCD40(-/-) mice.
- Inflammatory infiltrates were dominated by IgM-positive B cells, and mice exhibited anti-colon autoantibodies and elevated IFN-gamma.
Conclusions:
- Ectopic expression of CD40L on B cells can trigger intestinal inflammation, suggesting B cells can act as initiators of IBD.
- CD40-CD40L interaction is critical for the development of this B cell-mediated colitis.
- These findings highlight a potential role for B cells in the pathogenesis of human inflammatory bowel disease.