title: Cutting Edge: Ectopic expression of CD40 ligand on B cells induces lupus-like autoimmune disease.
abstract: CD40 ligand (CD40L) is ectopically expressed on B cells in patients with systemic lupus erythematosus (SLE) and lupus-prone BXSB mice. To assess the role of the ectopic CD40L expression in development of SLE, we have established transgenic mice expressing CD40L on B cells. Some of the 12- to 14-mo-old CD40L-transgenic mice spontaneously produced autoantibodies such as antinuclear Abs, anti-DNA Abs, and antihistone Abs. Moreover, approximately half of the transgenic mice developed glomerulonephritis with immune-complex deposition, whereas the kidneys of the normal littermates showed either no pathological findings or only mild histological changes. These results indicate that CD40L on B cells causes lupus-like disease in the presence of yet unknown environmental factors that by themselves do not induce the disease. Thus, ectopic CD40L expression on B cells may play a crucial role in development of SLE.
authors.affiliation: Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Higuchi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Aiba
authors.forename: Takashi
authors.initials: T
authors.lastname: Nomura
authors.forename: Junichiro
authors.initials: J
authors.lastname: Matsuda
authors.forename: Keiji
authors.initials: K
authors.lastname: Mochida
authors.forename: Misao
authors.initials: M
authors.lastname: Suzuki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kikutani
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Nishioka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsubata
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D004247:DNA / Q000276:immunology; D006657:Histones / Q000276:immunology; D007105:Immune Complex Diseases / Q000276:immunology / Q000473:pathology; D007668:Kidney / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic
chemical_list: D000974:Antibodies, Antinuclear; D006657:Histones; D023201:CD40 Ligand; D004247:DNA