Cutting Edge: Ectopic expression of CD40 ligand on B cells induces lupus-like autoimmune disease.
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.
Higuchi
Tetsuya
T
Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Aiba
Yuichi
Y
Nomura
Takashi
T
Matsuda
Junichiro
J
Mochida
Keiji
K
Suzuki
Misao
M
Kikutani
Hitoshi
H
Honjo
Tasuku
T
Nishioka
Kiyoshi
K
Tsubata
Takeshi
T
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
D000974:Antibodies, Antinuclear; D006657:Histones; D023201:CD40 Ligand; D004247:DNA