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Suppression of autoimmunity by CD5+ IL-10-producing B cells in lupus-prone mice

Genes & Immunity volume 16, pages 311–320 (2015)Cite this article

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Abstract

Systemic lupus erythematosus is a complex autoimmune disorder characterized by the production of pathogenic anti-nuclear antibodies. Previous work from our laboratory has shown that the introgression of a New Zealand Black-derived chromosome 4 interval onto a lupus-prone background suppresses the disease. Interestingly, the same genetic interval promoted the expansion of both Natural Killer T- and CD5+ B cells in suppressed mice. In this study, we show that ablation of NKT cells with a CD1d knockout had no impact on either the suppression of lupus or the expansion of CD5+ B cells. On the other hand, suppressed mice had an expanded population of IL-10-producing B cells that predominantly localized to the CD5+CD1dlow compartment. The expansion of CD5+ B cells negatively correlated with the frequency of pro-inflammatory IL-17 A-producing T-cells and kidney damage. Adoptive transfer with a single injection of total B cells with an enriched CD5+ compartment reduced the frequency of memory/activated, IFNγ-producing, and IL-17 A-producing CD4 T-cells but did not significantly reduce autoantibody levels. Taken together, these data suggest that the expansion of CD5+ IL-10-producing B cells and not NKT cells protects against lupus in these mice, by limiting the expansion of pro-inflammatory IL-17 A- and IFNγ-producing CD4 T-cells.

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Acknowledgements

This work was supported by a research grant from the Canadian Institutes of Health Research awarded to JW (FRN 102551). JW receives salary support from The Arthritis Centre of Excellence and the Arthritis Research Foundation of the University Health Network. YB is the recipient of a Canadian Institutes of Health Research Doctoral Research Award. KM is the recipient of an Ontario Graduate Scholarship. Special thanks to Eric Gracey for manuscript proofreading.

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Author notes

  1. C Loh

    Present address: 7Current Address: Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.,

Authors and Affiliations

  1. Department of Genetics and Development, Arthritis Center of Excellence, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada

    Y Baglaenko, K P Manion, N-H Chang, C Loh & J E Wither

  2. Department of Immunology, University of Toronto, Toronto, Ontario, Canada

    Y Baglaenko, K P Manion, C Loh & J E Wither

  3. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    G Lajoie

  4. Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada

    G Lajoie

  5. Department of Pathology, William Osler Health System, Brampton, Ontario, Canada

    G Lajoie

  6. Department of Medicine, University of Toronto, Toronto, Ontario, Canada

    J E Wither

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Correspondence to J E Wither.

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Baglaenko, Y., Manion, K., Chang, NH. et al. Suppression of autoimmunity by CD5+ IL-10-producing B cells in lupus-prone mice. Genes Immun 16, 311–320 (2015). https://doi.org/10.1038/gene.2015.17

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