Regulatory role of B-1 B cells in chronic colitis

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According to the ‘hygiene hypothesis’, enhanced microbial exposure due to early childhood infections leads to a reduction of Th2-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 Th2-mediated colitis under non-hygienic conditions, possibly by generating natural antibodies in response to microbial flora.

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