title: Suppression of autoimmunity by CD5(+) IL-10-producing B cells in lupus-prone 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(+)CD1d(low) 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.
authors.affiliation: 1] Arthritis Center of Excellence, Department of Genetics and Development, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada [2] Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Baglaenko
authors.affiliation: 1] Arthritis Center of Excellence, Department of Genetics and Development, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada [2] Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: K P
authors.initials: KP
authors.lastname: Manion
authors.affiliation: Arthritis Center of Excellence, Department of Genetics and Development, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: N-H
authors.initials: NH
authors.lastname: Chang
authors.affiliation: 1] Arthritis Center of Excellence, Department of Genetics and Development, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada [2] Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Loh
authors.affiliation: 1] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada [2] Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada [3] Department of Pathology, William Osler Health System, Brampton, Ontario, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Lajoie
authors.affiliation: 1] Arthritis Center of Excellence, Department of Genetics and Development, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada [2] Department of Immunology, University of Toronto, Toronto, Ontario, Canada [3] Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: J E
authors.initials: JE
authors.lastname: Wither
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018956:CD5 Antigens / Q000235:genetics / Q000378:metabolism*; D007156:Immunologic Memory; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008814:Mice, Inbred NZB
chemical_list: D018956:CD5 Antigens; D016753:Interleukin-10