Pathogenesis of lupus dermatoses in autoimmune mice. XIX. Attempts to induce subepidermal immunoglobulin deposition in MRL/Mp- +/+ mice.
The deposition of immunoglobulin (Ig) at the dermo-epidermal junction (DEJ) of the skin, frequently observed in autoimmune mouse strains, is similar to that seen in patients with systemic lupus erythematosus (SLE). MRL/Mp-lpr/lpr (MRL/lpr) mice have an autosomal recessive mutant gene, lpr, which produces massive T-cell proliferation and accelerates the onset of autoimmune diseases. MRL/Mp- +/+ (MRL/n) mice lack the lpr gene, and do not develop autoimmune disease during the first year after birth under pathogen-free conditions. To verify the mechanisms of subepidermal Ig deposition in the skin of LE, we designed an experiment in which we could induce Ig deposition in the control MRL/n mice. Intraperitoneal injection of lymphoproliferative cells of aged MRL/lpr mice induced splenomegaly and splenic granulomatous angitis in the control MRL/n mice. Lipopolysaccharide (LPS), a polyclonal B-cell activator, induced slight splenomegaly and relatively high levels of serum Ig. Dermatopathological investigation revealed mild lymphocyte infiltration without positive Ig deposition at the DEJ of MRL/n mice treated with proliferative T cells. Injection of both proliferative T cells and LPS induced 50% positivity of subepidermal Ig deposition, and high levels of serum immunoglobulins and anti-double stranded DNA (anti-dsDNA) antibodies. These changes were not observed in MRL/n mice injected with thymocytes of newborn MRL/lpr mice. Skin lesions and lupus nephritis were not demonstrated in any of the mice tested. This study suggest that both the mild inflammatory reaction and the presence of anti-dsDNA antibodies are required for the induction Ig deposition at the DEJ in the skin of LE patients.
Furukawa
F
F
Department of Dermatology, Faculty of Medicine, Kyoto University, Japan.
Ohshio
G
G
Imamura
S
S
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D005260:Female; D007136:Immunoglobulins / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D051379:Mice; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology
D000974:Antibodies, Antinuclear; D007136:Immunoglobulins