title: Abrogation of pathogenic IgG autoantibody production in CD40L gene-deleted lupus-prone New Zealand Black mice.
abstract: New Zealand Black (NZB) mice spontaneously develop a lupus-like autoimmune disease. Since CD40-CD40L interactions are important for B cell class-switch recombination and germinal center formation, we sought to understand the impact of these interactions on the immune abnormalities in NZB CD40L gene-deleted (CD40L(-/-)) mice in vivo. NZB.CD40L(-/-) mice demonstrated abrogation of all IgG autoantibodies tested and attenuated kidney disease. However, polyclonal B cell activation in vivo and B cell proliferation and class-switching in response to TLR ligands in vitro were preserved in the absence of CD40L in NZB mice. Although, plasmacytoid dendritic cell expansion and elevated BAFF production were unaffected by the absence of CD40L, there was some evidence that IFN-α-induced gene expression was reduced in the bone marrow of NZB.CD40L(-/-) mice. Our results suggest that CD40-CD40L interactions play an important role in promoting pathogenic IgG autoantibody production and kidney disease in NZB mice.
authors.affiliation: Arthritis Centre of Excellence, Toronto Western Research Institute, Toronto, Ontario, Canada. evelyn.pau@utoronto.ca
authors.forename: Evelyn
authors.initials: E
authors.lastname: Pau
authors.forename: Nan-Hua
authors.initials: NH
authors.lastname: Chang
authors.forename: Christina
authors.initials: C
authors.lastname: Loh
authors.forename: Ginette
authors.initials: G
authors.lastname: Lajoie
authors.forename: Joan E
authors.initials: JE
authors.lastname: Wither
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D015703:Antigens, CD / Q000378:metabolism; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D053264:B-Cell Activating Factor / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000502:physiology; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D016130:Immunophenotyping; D007370:Interferon Type I / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051193:Toll-Like Receptors / Q000819:agonists; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D001324:Autoantigens; D053264:B-Cell Activating Factor; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007370:Interferon Type I; C505720:Tnfsf13b protein, mouse; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand