title: A novel splenic B1 regulatory cell subset suppresses allergic disease through phosphatidylinositol 3-kinase-Akt pathway activation.
abstract: IL-10-producing regulatory B (B10) cells potently suppress allergic diseases, such as contact hypersensitivity (CHS). Splenic B10 cells share overlapping phenotypic markers with CD5+B1 B cells, CD1dhiCD21+CD23-marginal zone (MZ) B cells, and CD1dhiCD21+CD23+T2-MZ precursor B cells but do not exclusively belong to either subset.
  
  
  
  In this study we investigated the signaling mechanisms and a novel phenotypic parameter of B10 cells.
  
  
  
  We performed microarray analysis comparing IL-10+and IL-10-B cells. B cell-specific phosphatase and tensin homolog (PTEN)-deficient mice, which exhibit aberrant activation of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway in B cells, were examined.
  
  
  
  Microarray analysis revealed that the PI3K-Akt pathway is important for IL-10 production in B cells. PI3K-Akt pathway inhibitors reduced B10 cell numbers in vitro. B10 cell numbers were significantly increased in B cell-specific PTEN-deficient mice. The CHS response was significantly diminished in PTEN-deficient mice. Unexpectedly, splenic B10 cells in these mice were found within the B1 B-cell subset but not within the MZ B-cell subset. In wild-type mice not only MZ B10 cells but also B1-B10 cells were identified in the spleen. In addition, these 2 B10 cell subsets were predominantly found within the CD9+CD80+B-cell fraction.
  
  
  
  A novel splenic B1 regulatory cell subset (B1-B10 cells) was identified. Our findings show that the PI3K-Akt pathway in B cells is critical for B10 cell development and CHS response and that CD9/CD80 coexpression is a novel phenotypic parameter for both MZ-B10 and B1-B10 cells.
authors.affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan. Electronic address: t-matsushita@med.kanazawa-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsushita
authors.affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan; Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam.
authors.forename: Doanh
authors.initials: D
authors.lastname: Le Huu
authors.affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Hamaguchi
authors.affiliation: Department of Dermatology, University of Fukui, Fukui, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Exploratory Project on Cancer Stem Cells, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Naka
authors.affiliation: Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirao
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Muramatsu
authors.affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takehara
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tennodai, Tsukuba, Japan. Electronic address: fujimoto-m@umin.ac.jp.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006967:Hypersensitivity / Q000201:enzymology* / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D051379:Mice; D046228:Microarray Analysis; D058539:Phosphatidylinositol 3-Kinase / Q000276:immunology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D004791:Enzyme Inhibitors; D016753:Interleukin-10; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: B cells; B1 B cell; IL-10; Rodent; autoimmunity; marginal zone B cell; phosphatase and tensin homolog; phosphatidylinositol 3-kinase; regulatory B cell