Type i interferon-dependent CD86high marginal zone precursor b cells are potent T cell costimulators in mice

Academic Article

Abstract

  • Objective: To investigate the role of CD86high 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 IgGbright 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 3H-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 IgGbright 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. Conclusion: Type I IFN can promote autoimmune responses in BXD2 mice through up-regulation of CD86high 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. © 2011, American College of Rheumatology.
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    Digital Object Identifier (doi)

    Author List

  • Wang JH; Wu Q; Yang P; Li H; Li J; Mountz JD; Hsu HC
  • Start Page

  • 1054
  • End Page

  • 1064
  • Volume

  • 63
  • Issue

  • 4