Abrogation of Lupus Nephritis in Activation-Induced Deaminase-Deficient MRL/lpr Mice
| Autor: | Marilyn Diaz, Julie F. Foley, Ronald Herbert, Chuancang Jiang, Grace E. Kissling, Natasha P. Clayton, Micheal P. Jokinen |
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| Rok vydání: | 2007 |
| Předmět: |
Mice
Inbred MRL lpr Immunology B-Lymphocyte Subsets Lupus nephritis Kidney urologic and male genital diseases medicine.disease_cause Article Immunoglobulin G Autoimmunity Mice Species Specificity Cell Movement T-Lymphocyte Subsets immune system diseases Cytidine Deaminase medicine Activation-induced (cytidine) deaminase Animals Immunology and Allergy Lymphocyte Count skin and connective tissue diseases Autoantibodies Mice Knockout Mice Inbred BALB C biology medicine.disease Lupus Nephritis Survival Analysis Mice Inbred C57BL Mononuclear cell infiltration Immunoglobulin M Immunoglobulin class switching Organ Specificity Leukocytes Mononuclear biology.protein Nephritis |
| Zdroj: | The Journal of Immunology. 178:7422-7431 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | We generated MRL/lpr mice deficient in the Activation Induced Deaminase (AID). Because AID is required for immunoglobulin hypermutation and class switch recombination, these mice lack hypermutated IgG antibodies. 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 in AID-deficient mice translated into a dramatic reduction in glomerulonephritis, minimal mononuclear cell infiltration in the kidney, and a dramatic increase in survival to levels comparable to previously reported for MRL/lpr mice completely lacking B cells and levels well below those of mice lacking secreted antibodies. Therefore, this study, wherein littermates with either high levels of autoreactive IgM or autorective IgG are directly examined, proves that autoreactive IgM antibodies alone are not sufficient to promote kidney disease in MRL/lpr mice. In addition, the substantial decrease in mortality combined with a dramatic increase in autoreactive IgM antibodies in AID-deficient MRL/lpr mice, suggest that autoreactive IgM antibodies might not only fail to promote nephritis, but may also provide a protective role in MRL/lpr mice. This novel mouse model containing high levels of autoreactive, unmutated IgM antibodies will help delineate the contribution of autoreactive IgM to autoimmunity. |
| Databáze: | OpenAIRE |
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