ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Immune tolerance negatively regulates B cells in knock-in mice expressing broadly neutralizing HIV antibody 4E10.
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 81 papers.
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Who cites it
81 citing papers in PubMed, 98 citations in OpenAlex.
- Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes.The Journal of experimental medicine · 2019Trial
- High-Frequency, Functional HIV-Specific T-Follicular Helper and Regulatory Cells Are Present Within Germinal Centers in Children but Not Adults.Frontiers in immunology · 2018Trial
- Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals.Scientific reports · 2017Trial
- Naturally self-reactive B cells are poised to cross the selection barrier into autoimmune germinal centers.Cell reports · 2026Article
- Antibody Polyreactivity: A Challenger of Immune Paradigms.Immunology · 2025Review
- Viral glycoprotein-mediated entry and antibody-mediated immunity in HIV-1 and SARS-CoV-2 infection.Frontiers in immunology · 2025Review
- Affinity gaps among B cells in germinal centers drive the selection of MPER precursors.Nature immunology · 2024Article
- Vaccination induces broadly neutralizing antibody precursors to HIV gp41.Nature immunology · 2024Article
- In vivo affinity maturation of mouse B cells reprogrammed to express human antibodies.Nature biomedical engineering · 2024Article
- Central tolerance shapes the neutralizing B cell repertoire against a persisting virus in its natural host.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies.Nature reviews. Immunology · 2023Review
- Humanized V(D)J-rearranging and TdT-expressing mouse vaccine models with physiological HIV-1 broadly neutralizing antibody precursors.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Allelic polymorphism controls autoreactivity and vaccine elicitation of human broadly neutralizing antibodies against influenza virus.Immunity · 2022Article
- The Shaping of a B Cell Pool Maximally Responsive to Infections.Annual review of immunology · 2021Article
- HIV mRNA Vaccines-Progress and Future Paths.Vaccines · 2021Review
- Neutralizing Antibodies Targeting HIV-1 gp41.Viruses · 2020Review
- B cells expressing authentic naive human VRC01-class BCRs can be recruited to germinal centers and affinity mature in multiple independent mouse models.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Influenza vaccination strategies targeting the hemagglutinin stem region.Immunological reviews · 2020Review
- Conditional antibody expression to avoid central B cell deletion in humanized HIV-1 vaccine mouse models.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
A major goal of HIV research is to develop vaccines reproducibly eliciting broadly neutralizing Abs (bNAbs); however, this has proved to be challenging. One suggested explanation for this difficulty is that epitopes seen by bNAbs mimic self, leading to immune tolerance. We generated knock-in mice expressing bNAb 4E10, which recognizes the membrane proximal external region of gp41. Unlike b12 knock-in mice, described in the companion article (Ota et al. 2013. J. Immunol. 191: 3179-3185), 4E10HL mice were found to undergo profound negative selection of B cells, indicating that 4E10 is, to a physiologically significant extent, autoreactive. Negative selection occurred by various mechanisms, including receptor editing, clonal deletion, and receptor downregulation. Despite significant deletion, small amounts of IgM and IgG anti-gp41 were found in the sera of 4E10HL mice. On a Rag1⁻/⁻ background, 4E10HL mice had virtually no serum Ig of any kind. These results are consistent with a model in which B cells with 4E10 specificity are counterselected, raising the question of how 4E10 was generated in the patient from whom it was isolated. This represents the second example of a membrane proximal external region-directed bNAb that is apparently autoreactive in a physiological setting. The relative conservation in HIV of the 4E10 epitope might reflect the fact that it is under less intense immunological selection as a result of B cell self-tolerance. The safety and desirability of targeting this epitope by a vaccine is discussed in light of the newly described bNAb 10E8.
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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.