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.

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 ³H‐thymidine. The expression of CD86 and CD80 was determined by fluorescence‐activated cell sorting analysis.

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.

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.