title: Type I interferon-dependent CD86(high) marginal zone precursor B cells are potent T cell costimulators in mice.
abstract: OBJECTIVE
  To investigate the role of CD86(high) marginal zone (MZ) precursor B cells in type I interferon (IFN)-induced T cell-dependent responses in autoimmune BXD2 mice.
  
  
  METHODS
  Confocal microscopic imaging was used to determine the location of plasmacytoid dendritic cells (DCs), MZ precursor B cells, and CD4 T cells in the spleens of BXD2 and BXD2-Ifnar(-/-) mice. Immunohistochemical staining was used to determine IgG(bright) cells in the spleens of BXD2 and BXD2-Ifnar(-/-) mice. Enzyme-linked immunosorbent assay was used to determine serum levels of IFNα and autoantibodies, and 4-hydroxy-3-nitrophenylacetyl hapten (NP)-chicken γ-globulin (CGG) (NP-CGG)- or NP-Ficoll-induced anti-NP2 antibody titers. Real-time quantitative polymerase chain reaction was used to determine the levels of type I IFN transcripts. T cell proliferation was measured using (3) H-thymidine. The expression of CD86 and CD80 was determined by fluorescence-activated cell sorting analysis.
  
  
  RESULTS
  The deletion of type I IFN receptor abrogated the development of IgG(bright) cells and suppressed a T cell-dependent antibody response. Type I IFN signaling was associated with the expression of CD86, but not CD80, on follicular, MZ, and MZ precursor B cells. However, MZ precursor B cells demonstrated the highest expression of CD86 and the highest capacity for T cell costimulation with intact type I IFN receptor. This effect was blocked by an antibody that neutralizes CD86. In IFN receptor-intact BXD2 mouse spleens, MZ precursor B cells clustered at the T cell-B cell border. CD86 deletion suppressed germinal center formation, autoantibody production, and development of autoimmune diseases in BXD2 mice.
  
  
  CONCLUSIONS
  Type I IFN can promote autoimmune responses in BXD2 mice through up-regulation of CD86(high) expression on MZ precursor B cells and trafficking of MZ precursor B cells to the T cell-B cell border to provide costimulation of CD4 T cells.
authors.affiliation: University of Alabama, Birmingham, AL, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.forename: Pingar
authors.initials: P
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: John D
authors.initials: JD
authors.lastname: Mountz
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Hsu
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D018122:B7-1 Antigen / Q000502:physiology; D051940:B7-2 Antigen / Q000235:genetics / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007370:Interferon Type I / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007370:Interferon Type I