ArticleThe Journal of clinical investigation2001
Regulation of inherently autoreactive VH4-34 B cells in the maintenance of human B cell tolerance.
Article in The Journal of clinical investigation, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
168 citing papers in PubMed, 378 citations in OpenAlex.
- Failure of B Cell Tolerance in CVID.Frontiers in immunology · 2019Trial
- 9G4+ antibodies isolated from HIV-infected patients neutralize HIV-1 and have distinct autoreactivity profiles.PloS one · 2013Trial
- Effect of long-term belimumab treatment on B cells in systemic lupus erythematosus: extension of a phase II, double-blind, placebo-controlled, dose-ranging study.Arthritis and rheumatism · 2010Trial
- Uninflamed colonic tissue harbors humoral activity linked to anti-TNF therapy non-response in ulcerative colitis.iScience · 2026Article
- Evolution of self-reactive B cells: lessons from a lupus model.Biochemical Society transactions · 2026Review
- Progressive deterioration of adaptive immune repertoires in Down syndrome linked to interferon hyperactivity and lymphoid tissue disorganization.bioRxiv : the preprint server for biology · 2026Article
- B1 Cells for Life.Immunological reviews · 2026Review
- Increased VH4+JH6+ antibody heavy chain use in plasmablasts from asymptomatic multiple sclerosis patients.Genes and immunity · 2026Article
- Dysregulation of anti-Ro60 B cell autoreactivity in systemic lupus erythematosus.bioRxiv : the preprint server for biology · 2026Article
- Phage Display Technology: Design, Library Construction, and Panning Strategies for Antibody Development.Biomolecules & therapeutics · 2026Review
- Patient-Derived Monoclonal Myelin Oligodendrocyte Glycoprotein Autoantibodies Mediate Cytotoxicity.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- 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
- 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
- Diagnostics of Autoimmune Hepatitis Enabled by Non-Invasive Clinical Proteomics.Alimentary pharmacology & therapeutics · 2025Observational
- Clonal relationships between Tph and Tfh cells in patients with SLE and in murine lupus.Research square · 2025Article
- Clonal relationships between Tph and Tfh cells in patients with SLE and in murine lupus.bioRxiv : the preprint server for biology · 2025Article
- Sex Differences in B Cells From the Joints of Children With Oligoarticular Juvenile Idiopathic Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- IgMScientific reports · 2025Article
- Human naïve B cells show evidence of anergy and clonal redemption following vaccination.NPJ vaccines · 2025Article
- Disease diagnostics using machine learning of B cell and T cell receptor sequences.Science (New York, N.Y.) · 2025Article
108 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The study of human B cell tolerance has been hampered by difficulties in identifying a sizable population of autoreactive B lymphocytes whose fate could be readily determined. Hypothesizing that B cells expressing intrinsically autoreactive antibodies encoded by the VH4-34 heavy chain gene (VH4-34 cells) represent such a population, we tracked VH4-34 cells in healthy individuals. Here, we show that naive VH4-34 cells are positively selected and mostly restricted to the follicular mantle zone. Subsequently, these cells are largely excluded from the germinal centers and underrepresented in the memory compartment. In healthy donors but not in patients with systemic lupus erythematosus (SLE), these cells are prevented from differentiating into antibody-producing plasma cells. This blockade can be overcome ex vivo using cultures of naive and memory VH4-34 cells in the presence of CD70, IL-2, and IL-10. VH4-34 cells may therefore represent an experimentally useful surrogate for autoantibody transgenes and should prove valuable in studying human B cell tolerance in a physiological, polyclonal environment. Our initial results suggest that both positive and negative selection processes participate in the maintenance of tolerance in autoreactive human B cells at multiple checkpoints throughout B cell differentiation and that at least some censoring mechanisms are faulty in SLE.
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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.