ArticleThe Journal of experimental medicine2016
Clonal redemption of autoantibodies by somatic hypermutation away from self-reactivity during human immunization.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
What it found
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Who cites it
106 citing papers in PubMed, 145 citations in OpenAlex.
- Circulating autoreactive proteinase 3+ B cells and tolerance checkpoints in ANCA-associated vasculitis.JCI insight · 2021Trial
- Patients with common variable immunodeficiency with autoimmune cytopenias exhibit hyperplastic yet inefficient germinal center responses.The Journal of allergy and clinical immunology · 2019Trial
- BAFF and APRIL Receptors in B Cell Immunity and Autoimmunity.Immunological reviews · 2026Review
- B1 Cells for Life.Immunological reviews · 2026Review
- Longitudinal evolution of rheumatoid factor-expressing lymphoma precursors in a patient with Sjögren's disease.Journal of translational autoimmunity · 2026Article
- Defective B cell tolerance in SLE lymph nodes underpins VHmedRxiv : the preprint server for health sciences · 2026Article
- Germinal-centre and extrafollicular B cell pathways in systemic lupus erythematosus.Nature reviews. Rheumatology · 2026Review
- Virus-like antigen display delivers a stand-alone danger signal through the BCR that circumvents tolerance.bioRxiv : the preprint server for biology · 2026Article
- Naturally self-reactive B cells are poised to cross the selection barrier into autoimmune germinal centers.Cell reports · 2026Article
- Molecular mechanisms for direct sensing of virus-like antigens by B cells.International immunology · 2026Review
- Somatic deficiency of the human E3 ubiquitin ligase CBL in leukocytes impairs B cell but not T cell development and function.Nature immunology · 2026Article
- Framework-mediated binding of foreign and self-glycans by IGHV4-34 antibodies.Frontiers in immunology · 2026Review
- Convergent mutation trajectories convert functional self-tolerance in IGHV4-34 B cells to genetic tolerance encoded in the antibody.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Human naïve B cells show evidence of anergy and clonal redemption following vaccination.NPJ vaccines · 2025Article
- Self-reactive B cells are increased in all major stages of peripheral development in Sjögren's disease.Immunology and cell biology · 2025Article
- The role of polyreactive memory B cells in systemic lupus erythematosus.International immunology · 2025Review
- Defective germinal center selection results in persistence of self-reactive B cells from the primary to the secondary repertoire in Primary Antiphospholipid Syndrome.Nature communications · 2024Article
- Antibodies in neurological diseases: Established, emerging, explorative.Immunological reviews · 2024Review
- Autoimmune haemolytic anaemias.Nature reviews. Disease primers · 2024Review
- The common variable immunodeficiency IgM repertoire narrowly recognizes erythrocyte and platelet glycans.The Journal of allergy and clinical immunology · 2024Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clonal anergy is an enigmatic self-tolerance mechanism because no apparent purpose is served by retaining functionally silenced B cells bearing autoantibodies. Human autoantibodies with IGHV4-34*01 heavy chains bind to poly-N-acetyllactosamine carbohydrates (I/i antigen) on erythrocytes and B lymphocytes, cause cold agglutinin disease, and are carried by 5% of naive B cells that are anergic. We analyzed the specificity of three IGHV4-34*01 IgG antibodies isolated from healthy donors immunized against foreign rhesus D alloantigen or vaccinia virus. Each IgG was expressed and analyzed either in a hypermutated immune state or after reverting each antibody to its unmutated preimmune ancestor. In each case, the preimmune ancestor IgG bound intensely to normal human B cells bearing I/i antigen. Self-reactivity was removed by a single somatic mutation that paradoxically decreased binding to the foreign immunogen, whereas other mutations conferred increased foreign binding. These data demonstrate the existence of a mechanism for mutation away from self-reactivity in humans. Because 2.5% of switched memory B cells use IGHV4-34*01 and >43% of these have mutations that remove I/i binding, clonal redemption of anergic cells appears efficient during physiological human antibody responses.
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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.