Ectopic CD40 ligand expression on B cells triggers intestinal inflammation.
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.
Kawamura
Takahiro
T
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Kanai
Takanori
T
Dohi
Taeko
T
Uraushihara
Koji
K
Totsuka
Teruji
T
Iiyama
Ryoichi
R
Taneda
Chikara
C
Yamazaki
Motomi
M
Nakamura
Tetsuya
T
Higuchi
Tetsuya
T
Aiba
Yuichi
Y
Tsubata
Takeshi
T
Watanabe
Mamoru
M
D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D023201:CD40 Ligand / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000276:immunology / Q000473:pathology; D004760:Enterocolitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D007082:Ileum / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D019282:Wasting Syndrome / Q000235:genetics / Q000276:immunology / Q000473:pathology
D001323:Autoantibodies; D023201:CD40 Ligand