Journal
ARTHRITIS AND RHEUMATISM
Volume 63, Issue 4, Pages 1054-1064Publisher
WILEY-BLACKWELL
DOI: 10.1002/art.30231
Keywords
-
Categories
Funding
- American College of Rheumatology Research and Education Foundation
- Alliance for Lupus Research
- Department of Veterans Affairs [1I01BX000600-01]
- Daiichi-Sankyo Co., Ltd
- NIH [1-AI-071110-01A1, ARRA-3-R01-AI-71110-02S1, P30-AR-48311]
- Lupus Research Institute
- Arthritis Foundation
Ask authors/readers for more resources
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 IFN alpha and autoantibodies, and 4-hydroxy-3-nitrophenylacetyl hapten (NP)-chicken gamma-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 H-3-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 sup-pressed 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 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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available