title: Induction of ssDNA-binding autoantibody secreting B cell immunity during murine malaria infection is a critical part of the protective immune responses.
abstract: Although it has been hypothesized that autoimmune-like phenomena may play a critical role in the protective immune responses to both human and animal malaria, there are still no evidence-based data to support this view. In this study we demonstrate that the majority of anti-single stranded (ss) DNA autoantibody secreting B cells were confined to B220(+)CD21(+)CD23(-) cells and that these cells expanded significantly in the spleen of C57BL/6 mice infected with Plasmodium yoelii 17X non-lethal (PyNL). To determine the role of ssDNA-binding autoantibody secreting B cell responses in murine malaria, we conjugated generation 6 (poly) amidoamine dendrimer nanoparticles with ssDNA to deplete ssDNA-binding autoreactive B cells in vivo. Our data revealed that 55.5% of mice died after DNA-coated nanoparticle-mediated in vivo depletion of ssDNA-specific autoreactive B cells and subsequent challenge using PyNL. Adoptive transfer of B cells with ssDNA specificity to mice, followed by PyNL infection, caused a later appearance and inhibition of parasitemia. The possible mechanism by which the ssDNA-binding autoantibody secreting B cells is involved in the protection against murine malaria has also been demonstrated.
authors.affiliation: Department of Parasitology and International Health, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Kaiissar
authors.initials: K
authors.lastname: Mannoor
authors.forename: Changchun
authors.initials: C
authors.lastname: Li
authors.forename: Masashi
authors.initials: M
authors.lastname: Inafuku
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Toru
authors.initials: T
authors.lastname: Abo
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Sato
authors.forename: Hisami
authors.initials: H
authors.lastname: Watanabe
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D002478:Cells, Cultured; D004277:DNA, Single-Stranded / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007110:Immunity, Active / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D008212:Lymphocyte Depletion; D008288:Malaria / Q000276:immunology* / Q000628:therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage; D010967:Plasmodium yoelii / Q000276:immunology*; D013154:Spleen / Q000276:immunology*
chemical_list: D000974:Antibodies, Antinuclear; D004277:DNA, Single-Stranded