July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Loss of interferon regulatory factor 8 (IRF-8) in B cells promotes the expansion of regulatory B cells (Bregs) and suppresses intraocular autoimmune disease
Author Affiliations & Notes
  • Chengrong Yu
    Laboratory Immunology, National Eye Inst/NIH, Bethesda, Maryland, United States
  • Hyunsu Lee
    Laboratory Immunology, National Eye Inst/NIH, Bethesda, Maryland, United States
  • Daniel Gebreselasssie
    Laboratory Immunology, National Eye Inst/NIH, Bethesda, Maryland, United States
  • Jin Kyeong Choi
    Laboratory Immunology, National Eye Inst/NIH, Bethesda, Maryland, United States
  • Mary Mattapallil
    Laboratory Immunology, National Eye Inst/NIH, Bethesda, Maryland, United States
  • Favour Oladipupop
    Laboratory Immunology, National Eye Inst/NIH, Bethesda, Maryland, United States
  • Charles E Egwuagu
    Laboratory Immunology, National Eye Inst/NIH, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Chengrong Yu, None; Hyunsu Lee, None; Daniel Gebreselasssie, None; Jin Kyeong Choi, None; Mary Mattapallil, None; Favour Oladipupop, None; Charles Egwuagu, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2544. doi:
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      Chengrong Yu, Hyunsu Lee, Daniel Gebreselasssie, Jin Kyeong Choi, Mary Mattapallil, Favour Oladipupop, Charles E Egwuagu; Loss of interferon regulatory factor 8 (IRF-8) in B cells promotes the expansion of regulatory B cells (Bregs) and suppresses intraocular autoimmune disease. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2544.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : IRF-8 is implicated in the regulation of B-cell lineage commitment, activation, immunoglobulin gene recombination, and cytokine gene expression. In this study, we have generated mice with targeted deletion of IRF8 in B cells and have used the CD19-IRF-8KO (IRF-8KO) mice to investigated whether IRF-8 also plays a role in the development and/or expansion of regulatory B cells (Bregs) that regulate autoimmune diseases.

Methods : CD19-IRF-8KO mice were generated by cross-breeding CD19CRE with IRF8f/f mice. The conditional knockout mice were identified by tail DNA PCR. Targeted deletion of IRF8 in B cells of the IRF-8KO mice was ascertained by FACS, intracellular cytokine staining and Western blot analyses of peripheral CD19+ B cells. Immuno-phenotype of the IRF-8KO B cell was characterized by FACS analysis of B cell cell-surface proteins. We next examined whether loss of IRF8 in B cells would affect the generation/expansion of Breg cells during experimental autoimmune uveitis (EAU). We induced EAU by immunization with IRBP/CFA and established disease development by funduscopy and histology. Immune responses were analyzed by intracellular cytokine assay and ELISA. Lymphocyte proliferation was assessed by Thymidine incorporation.

Results : CD19-IRF-8KO mice exhibited marked reduction of follicular B cells (IgDhiCD21loCD23hi) and the expansion of marginal zone B cells with cell surface markers characteristic of Breg cells. Consistent with expansion of IL-10/IL-35-producing IRF-8KO Breg cells, IRF8-deficient mice are relatively resistant to EAU induction compared to WT counterparts.

Conclusions : Marginal B cells have strong regulatory function, suppress autoimmune responses and have long been suspected to be a major source of Breg populations. Our data showing that mice with loss of IRF-8 in B cells exhibit marked reduction of follicular B cells with concomitant expansion of marginal B cells, suggest that IRF-8 might promote humoral immunity, follicular cell and plasma cell development by antagonizing the alternative immune-suppressive developmental pathway orchestrated by marginal zone cells.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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