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Chuancang Jiang, Julie Foley, Natasha Clayton, Grace Kissling, Micheal Jokinen, Ronald Herbert, Marilyn Diaz, Abrogation of lupus nephritis in activation-induced cytidine deaminase-deficient MRL/lpr mice (130.3), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Page S228, https://doi.org/10.4049/jimmunol.178.Supp.130.3
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Abstract
Autoantibodies in systemic lupus erythematosus (SLE) patients and in mouse models of SLE are frequently found to be class switched and somatically mutated. To examine directly the role of hypermutated and isotype-switched antibodies in the pathogenesis of SLE, we generated a new MRL/lpr mouse strain deficient in the activation-induced cytidine deaminase (AID). Unlike their AID wild-type littermates, AID-deficient MRL/lpr mice not only lacked autoreactive IgG antibodies, but also experienced a dramatic increase in the levels of autoreactive IgM. This phenotype translated into a near abrogation of glomerulonephritis, minimal mononuclear cell infiltration in the kidneys, and a dramatic increase in survival, indicating that isotype-switched high affinity autoantibodies are required for the development of lupus nephritis. The dramatic decrease in mortality to levels well below levels previously reported for MRL/lpr mice lacking secreted antibodies, suggests that autoreactive IgM antibodies not only are insufficient in promoting kidney disease in MRL/lpr mice, but may also play a protective role.
This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.