title: Regulatory function of CpG-activated B cells in late-phase experimental allergic conjunctivitis.
abstract: OBJECTIVE
  To determine how CpG, an immunostimulatory sequence, affects experimental allergic conjunctivitis and to determine the mechanisms of its action.
  
  
  METHODS
  Experimental allergic conjunctivitis was induced in mice to investigate the suppressive mechanism of CpG treatment. Cytokine profiling, fluorescence-activated cell sorting analyses, and adoptive transfer were used to analyze suppressive mechanisms after CpG treatment.
  
  
  RESULTS
  Administration of the CpG oligonucleotide induced significant splenomegaly. Adoptive transfer of the splenocytes isolated from CpG-treated mice was able to confer resistance to allergen-induced inflammatory responses in recipient mice. CpG treatment led to a transient upregulation of IL-1ra, IL-18, IL-1alpha, and IL-12 in the spleen, draining lymph nodes, and conjunctiva. In contrast, IL-10 showed a marked and sustained induction in the inductive and effector tissues. Splenomegaly after CpG exposure was reduced in IL-10-deficient mice, indicating that IL-10 is required for immune remodeling of the spleen. Analyses of allergen-sensitized mice deficient in IL-10 exacerbated the late-phase inflammatory responses. Fluorescence-activated cell sorting analysis of the CpG-induced splenocyte subsets showed that the predominant source of IL-10 was B220(+) CD19(+) CD23(+)IgM(+)CD40(+)class II(high) follicular B cells. Adoptive transfer of IL-10-deficient B cells exacerbated eosinophilia. Transfer of an expanded population of cells after CpG treatment, including IL-10-secreting follicular B cells, protected against eosinophilia.
  
  
  CONCLUSIONS
  CpG treatment provided B cell-mediated regulation of immune responses and B cell differentiation in CpG-induced immune remodeling with the use of IL-10.
authors.affiliation: Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, 36-1 Nishicho Yonago, Tottori, Japan. dm@grape.med.tottori-u.ac.jp
authors.forename: Dai
authors.initials: D
authors.lastname: Miyazaki
authors.forename: Chuan Hui
authors.initials: CH
authors.lastname: Kuo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tominaga
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Inoue
authors.forename: Santa Jeremy
authors.initials: SJ
authors.lastname: Ono
mesh_terms: D000085:Acetates; D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology; D031164:Ambrosia; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D003233:Conjunctivitis, Allergic / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006969:Hypersensitivity, Immediate / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011058:Pollen / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013163:Splenomegaly / Q000139:chemically induced / Q000276:immunology
chemical_list: D000085:Acetates; D000485:Allergens; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C401286:SWR 0342SA