title: Role of regulatory B cells in chronic intestinal inflammation: association with pathogenesis of Crohn's disease.
abstract: The role of regulatory B cells (Bregs) producing interleukin (IL)-10 in the pathogenesis of inflammatory bowel diseases remains unknown. We investigated IL-10 production in B cells from patients with inflammatory bowel diseases and immunoregulatory functions of Bregs in experimental colitis mouse models. CpG DNA-induced IL-10 production in peripheral blood B cells isolated from patients with inflammatory bowel diseases and control subjects was examined. CD19 and CD1d were used for evaluating possible cell surface markers of Bregs. Colitis models of severe combined immunodeficiency mice were established by adoptive transfer of whole CD4 T cells or regulatory T cell (Treg)-depleted T cells (CD4CD25) isolated from SAMP1/Yit mice and the function of Bregs in intestinal inflammation was elucidated by evaluating the effects of cotransfer of whole or Breg-depleted B cells. CpG DNA-induced IL-10 production was significantly decreased in B cells from patients with Crohn's disease (CD), as compared with those from healthy controls, whereas Bregs were found to be enriched in a population of CD19 and CD1d B cells isolated from both human and mouse samples. The severity of intestinal inflammation was significantly increased in the Breg-depleted mice, with similar results also found in adoptive transfer colitis model mice even after Treg depletion. Our findings show that Bregs, characterized by the cell surface markers CD19 and CD1d, significantly reduced experimental colitis regardless of the presence or absence of Tregs. These results suggest that a deficiency or decrease of Bregs function exacerbates intestinal inflammation, which may be associated with the pathogenesis of CD.
authors.affiliation: *Department of Internal Medicine II, Shimane University School of Medicine, Shimane, Japan; †Division of Gastrointestinal Endoscopy, Shimane University Hospital, Shimane, Japan; and ‡Yakult Central Institute for Microbiological Research, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Oka
authors.forename: Shunji
authors.initials: S
authors.lastname: Ishihara
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mishima
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Tada
authors.forename: Ryusaku
authors.initials: R
authors.lastname: Kusunoki
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Fukuba
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yuki
authors.forename: Kousaku
authors.initials: K
authors.lastname: Kawashima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D060151:B-Lymphocytes, Regulatory; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID
chemical_list: D016753:Interleukin-10