ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Molecular basis of 9G4 B cell autoreactivity in human systemic lupus erythematosus.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Organ-based characterization of B cells in patients with systemic lupus erythematosus.Frontiers in immunology · 2025Pooled it
- Failure of B Cell Tolerance in CVID.Frontiers in immunology · 2019Trial
- Redemption of autoantibodies on anergic B cells by variable-region glycosylation and mutation away from self-reactivity.Proceedings of the National Academy of Sciences of the United States of America · 2014Trial
- 9G4+ antibodies isolated from HIV-infected patients neutralize HIV-1 and have distinct autoreactivity profiles.PloS one · 2013Trial
- Single-Cell Level Characterization of B Cell Depletion and Repopulation Following Rituximab in Systemic Lupus Erythematosus.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Autoreactive B cells in systemic lupus erythematosus: insights from integrative multi-omics analyses.Inflammation and regeneration · 2026Review
- 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
- Plasmablast Storms: Microbial Drivers of Acute and Chronic Autoimmune Flares.Microorganisms · 2026Review
- Framework-mediated binding of foreign and self-glycans by IGHV4-34 antibodies.Frontiers in immunology · 2026Review
- Recurrent antibody repertoire features associated with six selected human IGHV genes: V(D)J usage, heavy-light pairing, and CDRH3 properties.Frontiers in immunology · 2026Article
- Precision targeting of autoreactive B cells in systemic lupus erythematosus using anti-9G4 idiotope synthetic immune receptor T cells.bioRxiv : the preprint server for biology · 2025Article
- Human naïve B cells show evidence of anergy and clonal redemption following vaccination.NPJ vaccines · 2025Article
- The role of polyreactive memory B cells in systemic lupus erythematosus.International immunology · 2025Review
- Hypomorphic RAG2 Deficiency Promotes Selection of Self-Reactive B Cells.Journal of clinical immunology · 2025Article
- 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
- Transposon DNA sequences facilitate the tissue-specific gene transfer of circulating tumor DNA between human cells.Nucleic acids research · 2024Article
- NADPH oxidase exerts a B cell-intrinsic contribution to lupus risk by modulating endosomal TLR signals.The Journal of experimental medicine · 2024Article
- B cell receptor repertoire abnormalities in autoimmune disease.Frontiers in immunology · 2024Review
- A retrotransposon-derived DNA zip code internalizes myeloma cells through Clathrin-Rab5a-mediated endocytosis.Frontiers in oncology · 2024Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
9G4(+) IgG Abs expand in systemic lupus erythematosus (SLE) in a disease-specific fashion and react with different lupus Ags including B cell Ags and apoptotic cells. Their shared use of VH4-34 represents a unique system to understand the molecular basis of lupus autoreactivity. In this study, a large panel of recombinant 9G4(+) mAbs from single naive and memory cells was generated and tested against B cells, apoptotic cells, and other Ags. Mutagenesis eliminated the framework-1 hydrophobic patch (HP) responsible for the 9G4 idiotype. The expression of the HP in unselected VH4-34 cells was assessed by deep sequencing. We found that 9G4 Abs recognize several Ags following two distinct structural patterns. B cell binding is dependent on the HP, whereas anti-nuclear Abs, apoptotic cells, and dsDNA binding are HP independent and correlate with positively charged H chain third CDR. The majority of mutated VH4-34 memory cells retain the HP, thereby suggesting selection by Ags that require this germline structure. Our findings show that the germline-encoded HP is compulsory for the anti-B cell reactivity largely associated with 9G4 Abs in SLE but is not required for reactivity against apoptotic cells, dsDNA, chromatin, anti-nuclear Abs, or cardiolipin. Given that the lupus memory compartment contains a majority of HP(+) VH4-34 cells but decreased B cell reactivity, additional HP-dependent Ags must participate in the selection of this compartment. This study represents the first analysis, to our knowledge, of VH-restricted autoreactive B cells specifically expanded in SLE and provides the foundation to understand the antigenic forces at play in this disease.
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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.