title: Selective Memory to Apoptotic Cell-Derived Self-Antigens with Implications for Systemic Lupus Erythematosus Development.
abstract: Autoimmune diseases are characterized by pathogenic immune responses to self-antigens. In systemic lupus erythematosus (SLE), many self-antigens are found in apoptotic cells (ACs), and defects in removal of ACs from the body are linked to a risk for developing SLE. This includes pathological memory that gives rise to disease flares. In this study, we investigated how memory to AC-derived self-antigens develops and the contribution of self-memory to the development of lupus-related pathology. Multiple injections of ACs without adjuvant into wild-type mice induce a transient primary autoimmune response without apparent anti-nuclear Ab reactivity or kidney pathology. Interestingly, as the transient Ab response reached baseline, a single boost injection fully recalled the immune response to ACs, and this memory response was furthermore transferable into naive mice. Additionally, the memory response contains elements of pathogenicity, accompanied by selective memory to selective Ags. Thus, we provide evidence for a selective self-memory that underlies progression of the response to self-antigens with implications for SLE development therapy.
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors: Amanda
authors: 0000-0003-1504-4789
authors: A
authors: Duhlin
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors: Yunying
authors: Y
authors: Chen
authors: Department of Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden; and.
authors: Fredrik
authors: 0000-0001-9633-677X
authors: F
authors: Wermeling
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors: Saikiran K
authors: SK
authors: Sedimbi
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors: Emma
authors: E
authors: Lindh
authors: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 2M9, Canada.
authors: Rahul
authors: 0000-0001-8767-5032
authors: R
authors: Shinde
authors: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 2M9, Canada.
authors: Marie Jo
authors: MJ
authors: Halaby
authors: Department of Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden; and.
authors: Ylva
authors: Y
authors: Kaiser
authors: Department of Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden; and.
authors: Ola
authors: O
authors: Winqvist
authors: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 2M9, Canada.
authors: Tracy L
authors: TL
authors: McGaha
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; mikael.karlsson@ki.se.
authors: Mikael C I
authors: MC
authors: Karlsson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001323:Autoantibodies; D001324:Autoantigens