ArticleArthritis and rheumatism2011
Activation-induced deaminase-deficient MRL/lpr mice secrete high levels of protective antibodies against lupus nephritis.
Article in Arthritis and rheumatism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- The immunology of B-1 cells: from development to aging.Immunity & ageing : I & A · 2024Review
- Natural autoimmunity in oligoarticular juvenile idiopathic arthritis.Pediatric rheumatology online journal · 2023Article
- Involvement of IL-33 in the Pathophysiology of Systemic Lupus Erythematosus: Review.International journal of molecular sciences · 2022Review
- New insights on the role of human leukocyte antigen complex in primary biliary cholangitis.Frontiers in immunology · 2022Review
- The Role of IgM Antibodies in T Cell Lymphoma Protection in a Novel Model Resembling Anaplastic Large Cell Lymphoma.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Relationship between natural and infection-induced antibodies in systemic autoimmune diseases (SAD): SLE, SSc and RA.Clinical and experimental immunology · 2021Article
- Early Treatment of Interleukin-33 can Attenuate Lupus Development in Young NZB/W F1 Mice.Cells · 2020Article
- Abrogated AID Function Prolongs Survival and Diminishes Renal Pathology in the BXSB Mouse Model of Systemic Lupus Erythematosus.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Signaling control of antibody isotype switching.Advances in immunology · 2019Review
- Anti-double Stranded DNA Antibodies: Origin, Pathogenicity, and Targeted Therapies.Frontiers in immunology · 2019Review
- A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows.BMC genomics · 2018Article
- Accelerated Systemic Autoimmunity in the Absence of Somatic Hypermutation in 564Igi: A Mouse Model of Systemic Lupus with Knocked-In Heavy and Light Chain Genes.Frontiers in immunology · 2017Article
- Autoantibodies in SLE: Specificities, Isotypes and Receptors.Antibodies (Basel, Switzerland) · 2016Review
- Natural IgM and the Development of B Cell-Mediated Autoimmune Diseases.Critical reviews in immunology · 2016Review
- Altered BCR and TLR signals promote enhanced positive selection of autoreactive transitional B cells in Wiskott-Aldrich syndrome.The Journal of experimental medicine · 2015Article
- Predominant role for activation-induced cytidine deaminase in generating IgG anti-nucleosomal antibodies of murine SLE.Journal of autoimmunity · 2015Article
- Mechanisms of Kidney Injury in Lupus Nephritis - the Role of Anti-dsDNA Antibodies.Frontiers in immunology · 2015Review
- Histone deacetylase inhibitors upregulate B cell microRNAs that silence AID and Blimp-1 expression for epigenetic modulation of antibody and autoantibody responses.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Natural IgM: beneficial autoantibodies for the control of inflammatory and autoimmune disease.Journal of clinical immunology · 2014Review
- Common tolerance mechanisms, but distinct cross-reactivities associated with gp41 and lipids, limit production of HIV-1 broad neutralizing antibodies 2F5 and 4E10.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveWe previously generated MRL/lpr mice deficient in activation-induced deaminase (AID) that lack isotype switching and immunoglobulin hypermutation. These mice have high levels of unmutated (germline) autoreactive IgM, yet they experienced an increase in survival and an improvement in lupus nephritis that exceeded that of MRL/lpr mice lacking IgG. The purpose of the present study was to test the hypothesis that high levels of germline autoreactive IgM in these mice confer protection against lupus nephritis.
methodsAutoreactive IgM antibodies of various specificities, including antibodies against double-stranded DNA (dsDNA), from AID-deficient MRL/lpr mice were given to asymptomatic MRL/lpr mice, and the levels of cytokines, proteinuria, immune complex deposition in the kidneys, and glomerulonephritis were examined. Novel AID-deficient MRL/lpr mice that lack any antibodies were generated for comparison to AID-deficient MRL/lpr mice that secrete only IgM.
resultsTreatment with IgM anti-dsDNA resulted in a dramatic improvement in lupus nephritis. Other autoreactive IgM antibodies, such as antiphospholipid and anti-Sm, did not alter the pathologic changes. Secretion of proinflammatory cytokines by macrophages and the levels of inflammatory cells and apoptotic debris in the kidneys were lower in mice receiving IgM anti-dsDNA. Protective IgM derived from AID-deficient MRL/lpr mice displayed a distinct B cell repertoire, with a bias toward members of the V(H) 7183 family.
conclusionIgM anti-dsDNA protected MRL/lpr mice from lupus nephritis, likely by stopping the inflammatory cascade leading to kidney damage. A distinct repertoire of V(H) usage in IgM anti-dsDNA hybridomas from AID-deficient mice suggests that there is enrichment of a dedicated B cell population that secretes unmutated protective IgM in these mice.
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Registered trials
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