title: Idiotype-specific Th cells support oligoclonal expansion of anti-dsDNA B cells in mice with lupus.
abstract: Systemic lupus erythematosus (SLE) is marked by a Th cell-dependent B cell hyperresponsiveness, with frequent germinal center reactions and hypergammaglobulinemia. The specificity of Th cells in lupus remains unclear, but B cell Ids have been suggested. A hallmark is the presence of anti-dsDNA, mutated IgG autoantibodies with a preponderance of arginines in CDR3 of the Ig variable H chain (IgVH). B cells can present V region-derived Id peptides on their MHC class II molecules to Id-specific Th cells. We show that Id-specific Th cells support the proliferation of anti-dsDNA Id(+) B cells in mice suffering from systemic autoimmune disease with SLE-like features. Mice developed marked clonal expansions of B cells; half of the IgVH sequences were clonally related. Anti-dsDNA B cells made up 40% of B cells in end-stage disease. The B cells expressed mutated IgVH with multiple arginines in CDR3. Hence, Id-driven T cell-B cell collaboration supported the production of classical anti-dsDNA Abs, recapitulating the characteristics of such Abs in SLE. The results support the concept that Id-specific Th cells may trigger the development of SLE and suggest that manipulation of the Id-specific T cell repertoire could play a role in treatment.
authors.affiliation: Centre for Immune Regulation, Department of Immunology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, 0424 Oslo, Norway; and kristin.aas-hanssen@medisin.uio.no bjarne.bogen@medisin.uio.no l.a.munthe@medisin.uio.no.
authors.forename: Kristin
authors.initials: K
authors.lastname: Aas-Hanssen
authors.affiliation: Centre for Immune Regulation, Department of Immunology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, 0424 Oslo, Norway; and.
authors.forename: Ane
authors.initials: A
authors.lastname: Funderud
authors.affiliation: Centre for Immune Regulation, Department of Immunology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, 0424 Oslo, Norway; and.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Thompson
authors.affiliation: Centre for Immune Regulation, Department of Immunology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, 0424 Oslo, Norway; and K.G. Jebsen Centre for Influenza Vaccine Research, Department of Immunology, Oslo University Hospital, University of Oslo, 0424 Oslo, Norway kristin.aas-hanssen@medisin.uio.no bjarne.bogen@medisin.uio.no l.a.munthe@medisin.uio.no.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.affiliation: Centre for Immune Regulation, Department of Immunology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, 0424 Oslo, Norway; and kristin.aas-hanssen@medisin.uio.no bjarne.bogen@medisin.uio.no l.a.munthe@medisin.uio.no.
authors.forename: Ludvig A
authors.initials: LA
authors.lastname: Munthe
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000276:immunology*; D001120:Arginine / Q000737:chemistry; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D060966:Clonal Selection, Antigen-Mediated / Q000276:immunology*; D004247:DNA / Q000276:immunology*; D006942:Hypergammaglobulinemia / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D017422:Sequence Analysis, DNA; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D004247:DNA; D001120:Arginine