1. Suppression of autoimmunity by CD5+ IL-10-producing B cells in lupus-prone mice.
- Author
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Baglaenko, Y, Manion, K P, Chang, N-H, Loh, C, Lajoie, G, and Wither, J E
- Subjects
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AUTOIMMUNITY , *CD5 antigen , *INTERLEUKIN-10 , *KILLER cells , *SYSTEMIC lupus erythematosus treatment , *LABORATORY mice - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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