ArticleThe EMBO journal2021
Memory IgM protects endogenous insulin from autoimmune destruction.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Differential Contributions of IgM and IgG Autoantibodies to Serologic IA2 Reactivity in Type 1 Diabetes.Biomolecules · 2026Article
- Inverted insulin to C-Peptide ratios in neonatal intensive care: is there something we don't know?Frontiers in pediatrics · 2026Article
- T-betNature communications · 2024Article
- TLR7 and IgM: Dangerous Partners in Autoimmunity.Antibodies (Basel, Switzerland) · 2023Review
- Review
- Isotype-specific plasma cells express divergent transcriptional programs.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Autoreactive antibodies control blood glucose by regulating insulin homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Rheumatoid factor IgM autoantibodies control IgG homeostasis.Frontiers in immunology · 2022Article
- Toll-like receptor agonist combinations augment mouse T-cell anti-tumor immunity via IL-12- and interferon ß-mediated suppression of immune checkpoint receptor expression.Oncoimmunology · 2022Article
- Memory IgM protects endogenous insulin from autoimmune destruction.The EMBO journal · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The enormous diversity of antibody specificities is generated by random rearrangement of immunoglobulin gene segments and is important for general protection against pathogens. Since random rearrangement harbors the risk of producing self-destructive antibodies, it is assumed that autoreactive antibody specificities are removed during early B-cell development leading to a peripheral compartment devoid of autoreactivity. Here, we immunized wild-type mice with insulin as a common self-antigen and monitored diabetes symptoms as a measure for autoimmune disease. Our results show that autoreactive anti-insulin IgM and IgG antibodies associated with autoimmune diabetes can readily be generated in wild-type animals. Surprisingly, recall immunizations induced increased titers of high-affinity insulin-specific IgM, which prevented autoimmune diabetes. We refer to this phenomenon as adaptive tolerance, in which high-affinity memory IgM prevents autoimmune destruction by competing with self-destructive antibodies. Together, this study suggests that B-cell tolerance is not defined by the absolute elimination of autoreactive specificities, as harmful autoantibody responses can be generated in wild-type animals. In contrast, inducible generation of autoantigen-specific affinity-matured IgM acts as a protective mechanism preventing self-destruction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.