TY - JOUR
T1 - Regulatory role of B-1 B cells in chronic colitis
AU - Shimomura, Yasuyo
AU - Mizoguchi, Emiko
AU - Sugimoto, Ken
AU - Kibe, Ryoko
AU - Benno, Yoshimi
AU - Mizoguchi, Atsushi
AU - Bhan, Atul K.
N1 - Funding Information:
National Institutes of Health (DK47677 to A.K.B., DK064351 and the Eli and Edythe L. Broad Medical Research Program to A.M., DK64289 and DK74454 to E.M.); Research Fellowship Award from Crohn’s and Colitis Foundation of America to K.S.; Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital (DK43351).
PY - 2008/6
Y1 - 2008/6
N2 - According to the 'hygiene hypothesis', enhanced microbial exposure due to early childhood infections leads to a reduction of Th 2-mediated allergic diseases and inflammatory bowel disease. To begin to elucidate the mechanisms underlying this hypothesis, we studied development of Th2-mediated colitis of the TCRα knockout (KO) mouse in both a specific pathogen-free (SPF) facility and a conventional (CV) facility. After more than five generations in each facility, TCRα KO mice kept in the CV facility developed dramatically less colitis than mice that were kept in the SPF facility. Surprisingly, the suppression of colitis in the CV facility correlated with a significant increase in natural IgM production by B-1 B cells. In contrast, B cell-deficient TCRα double-knockout (αμ DKO) mice maintained in the CV facility continued to develop severe colitis, strongly suggesting that B-1 B cells contributed to the suppression of colitis. Indeed, the adoptive transfer of B-1 B cells isolated from the peritoneal cavity of TCRα KO mice (SPF) into αμ DKO mice (CV) suppressed the development of colitis in the recipient mice. We conclude that B-1 cells play a regulatory role in Th 2-mediated colitis under non-hygienic conditions, possibly by generating natural antibodies in response to microbial flora.
AB - According to the 'hygiene hypothesis', enhanced microbial exposure due to early childhood infections leads to a reduction of Th 2-mediated allergic diseases and inflammatory bowel disease. To begin to elucidate the mechanisms underlying this hypothesis, we studied development of Th2-mediated colitis of the TCRα knockout (KO) mouse in both a specific pathogen-free (SPF) facility and a conventional (CV) facility. After more than five generations in each facility, TCRα KO mice kept in the CV facility developed dramatically less colitis than mice that were kept in the SPF facility. Surprisingly, the suppression of colitis in the CV facility correlated with a significant increase in natural IgM production by B-1 B cells. In contrast, B cell-deficient TCRα double-knockout (αμ DKO) mice maintained in the CV facility continued to develop severe colitis, strongly suggesting that B-1 B cells contributed to the suppression of colitis. Indeed, the adoptive transfer of B-1 B cells isolated from the peritoneal cavity of TCRα KO mice (SPF) into αμ DKO mice (CV) suppressed the development of colitis in the recipient mice. We conclude that B-1 cells play a regulatory role in Th 2-mediated colitis under non-hygienic conditions, possibly by generating natural antibodies in response to microbial flora.
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U2 - 10.1093/intimm/dxn031
DO - 10.1093/intimm/dxn031
M3 - Article
C2 - 18375938
AN - SCOPUS:44849114332
SN - 0953-8178
VL - 20
SP - 729
EP - 737
JO - International Immunology
JF - International Immunology
IS - 6
ER -