The genotype of mice influences the autoimmune response to spliceosome proteins induced by cytomegalovirus gB immunization.
In previous studies we have established a link between cytomegalovirus (CMV) infection and an autoimmune response to the U1-70 k protein of the spliceosome in man. This autoimmune response, generally referred to as the anti-RNP (ribonucleoprotein) antibodies, is observed in about 30% of patients with systemic lupus erythematosus (SLE). We have also found that the CMV glycoprotein B (CMV gB) when expressed in a adenovirus vector (Ad) could induce a significant anti-U1-70 k antibody response in several strains of mice, such as C3H, MRL and BALB/c. In the present study we examined the autoimmune response induced by immunization with Ad-gB in A/J and C57BL/6 (B6) mice and determined whether there was any autoimmune phenotype similar to that observed in patients with SLE. Thus groups of A/J and B6 mice were immunized with Ad/gB or with Ad alone and then observed for possible skin or kidney disease. In addition the autoantibody response to the spliceosome was measured, and the target antigens identified by immunoblot techniques. All of the A/J mice mounted a very high IgG response primarily to the U1-70 k protein of the spliceosome, with evidence of a rapid spreading of the autoantibody response to other components of the complex. In contrast, B6 mice mounted only a very low titre autoantibody response and failed to show signs or symptoms of autoimmunity. The A/J but not the B6 mice were found to have deposits of IgG in their kidneys, which were consistent with abnormal levels of blood urea nitrogen in the A/J but not B6 mice. This study demonstrates the importance of the genetic background in the susceptibility to autoimmunity.
Lipes
J
J
Department of Medicine, The McGill University Hospital Center Research Institute, The Montreal General Hospital, Canada.
Skamene
E
E
Newkirk
M M
MM
D000256:Adenoviridae / Q000276:immunology; D000818:Animals; D020296:Animals, Congenic; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000032:analysis; D000956:Antigens, Viral / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D005822:Genetic Vectors / Q000276:immunology; D005838:Genotype; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology; D007668:Kidney / Q000276:immunology / Q000503:physiopathology; D008181:Lupus Nephritis / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A / Q000235:genetics / Q000276:immunology*; D008810:Mice, Inbred C57BL / Q000235:genetics / Q000276:immunology*; D011507:Proteinuria / Q000209:etiology / Q000276:immunology; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000276:immunology*; D012867:Skin / Q000276:immunology / Q000473:pathology; D017381:Spliceosomes / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D000936:Antigen-Antibody Complex; D000956:Antigens, Viral; D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D017412:Ribonucleoprotein, U1 Small Nuclear; C490688:SNRNP70 protein, human; C490687:Snrnp70 protein, mouse; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus