Regulatory role of B-1 B cells in chronic colitis.
According to the 'hygiene hypothesis', enhanced microbial exposure due to early childhood infections leads to a reduction of T(h)2-mediated allergic diseases and inflammatory bowel disease. To begin to elucidate the mechanisms underlying this hypothesis, we studied development of T(h)2-mediated colitis of the TCRalpha knockout (KO) mouse in both a specific pathogen-free (SPF) facility and a conventional (CV) facility. After more than five generations in each facility, TCRalpha 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 TCRalpha double-knockout (alphamu 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 TCRalpha KO mice (SPF) into alphamu DKO mice (CV) suppressed the development of colitis in the recipient mice. We conclude that B-1 cells play a regulatory role in T(h)2-mediated colitis under non-hygienic conditions, possibly by generating natural antibodies in response to microbial flora.
Shimomura
Yasuyo
Y
Experimental Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Mizoguchi
Emiko
E
Sugimoto
Ken
K
Kibe
Ryoko
R
Benno
Yoshimi
Y
Mizoguchi
Atsushi
A
Bhan
Atul K
AK
D019264:Adoptive Transfer; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology* / Q000382:microbiology; D005434:Flow Cytometry; D005856:Germ-Free Life; D007075:Immunoglobulin M; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000517:prevention & control; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D010529:Peritoneal Cavity / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology*
D039481:CD11b Antigen; D007075:Immunoglobulin M