Homeostatic regulation of intestinal villous epithelia by B lymphocytes.
The epithelial cell of the small intestine is one of the most rapidly regenerating cells in the body. However, the cellular mechanism and biological significance underlying this rapid regeneration remain elusive. In this study we examined the intestinal epithelia of mutant mice that lack B and/or T cells and those of normal littermates. The absence of B cells in Ig mu-chain mutant mice or B and T cells in recombination-activating gene (RAG)-2(-/-) as well as SCID mutant mice was associated with a marked acceleration of epithelial cell turnover and an up-regulation of the expression of MHC class II molecules. No such effects were observed in T cell-deficient TCR-delta and -beta double-mutant mice. As far as the goblet cells of villous epithelium are concerned, absolute numbers of them remained the same among these mutant mice that have no B and/or T cells. Alymphoplasia (aly/aly) mutant mice that lacked Peyer's patches and Ig-producing cells in the lamina propria, but harbored a large number of intestinal mucosal T cells, also displayed a significant acceleration of epithelial cell turnover and, to some extent, up-regulated expression of MHC class II molecules. Notably, the accelerated epithelial cell turnover was not observed and returned to normalcy in the Ig mu-chain mutant mice that had been given antibiotic-containing water. These findings indicate that B cells down-regulate the generation and differentiation of intestinal epithelial cells in the normal wild-type condition and suggest that enteric microorganisms are implicated in the accelerated generation of epithelial cells in mice that have no B cells.
Nishiyama
Yasuhiro
Y
Department of Microbiology, Keio University School of Medicine, Nippon Medical School, Tokyo, Japan.
Hamada
Hiromasa
H
Nonaka
Satoshi
S
Yamamoto
Hiroshi
H
Nanno
Masanobu
M
Katayama
Yasuo
Y
Takahashi
Hidemi
H
Ishikawa
Hiromichi
H
D000667:Ampicillin / Q000008:administration & dosage; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D019674:Genes, T-Cell Receptor beta / Q000235:genetics / Q000276:immunology; D019676:Genes, T-Cell Receptor delta / Q000235:genetics / Q000276:immunology; D020397:Goblet Cells / Q000166:cytology / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D015378:Imipenem / Q000008:administration & dosage; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000473:pathology; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D008871:Microvilli / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D015378:Imipenem; D000667:Ampicillin