ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Common tolerance mechanisms, but distinct cross-reactivities associated with gp41 and lipids, limit production of HIV-1 broad neutralizing antibodies 2F5 and 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 65 papers.
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Who cites it
65 citing papers in PubMed, 83 citations in OpenAlex.
- Self-tolerance curtails the B cell repertoire to microbial epitopes.JCI insight · 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
- Maturation of HIV-1 neutralizing antibodies in a germinal center conditional expression mouse model.PLoS pathogens · 2026Article
- Naturally self-reactive B cells are poised to cross the selection barrier into autoimmune germinal centers.Cell reports · 2026Article
- An HIV-1 gp41 peptide-liposome vaccine elicits neutralizing epitope-targeted antibody responses in healthy individuals.medRxiv : the preprint server for health sciences · 2025Article
- Viral glycoprotein-mediated entry and antibody-mediated immunity in HIV-1 and SARS-CoV-2 infection.Frontiers in immunology · 2025Review
- Article
- 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
- 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
- Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions.Cell reports. Medicine · 2023Article
- 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
- B cells expressing IgM B cell receptors of HIV-1 neutralizing antibodies discriminate antigen affinities by sensing binding association rates.Cell reports · 2022Article
- 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
- B Cells Carrying Antigen Receptors Against Microbes as Tools for Vaccine Discovery and Design.Current topics in microbiology and immunology · 2020Review
- Cross-Reactivity to Kynureninase Tolerizes B Cells That Express the HIV-1 Broadly Neutralizing Antibody 2F5.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Targeted selection of HIV-specific antibody mutations by engineering B cell maturation.Science (New York, N.Y.) · 2019Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Developing an HIV-1 vaccine has been hampered by the inability of immunogens to induce broadly neutralizing Abs (BnAbs) that protect against infection. Previously, we used knockin (KI) mice expressing a prototypical gp41-specific BnAb, 2F5, to demonstrate that immunological tolerance triggered by self-reactivity of the 2F5 H chain impedes BnAb induction. In this study, we generate KI models expressing H chains from two other HIV-1 Abs, 4E10 (another self-/polyreactive, anti-gp41 BnAb) and 48d (an anti-CD4 inducible, nonpolyreactive Ab), and find a similar developmental blockade consistent with central B cell deletion in 4E10, but not in 48d VH KI mice. Furthermore, in KI strains expressing the complete 2F5 and 4E10 Abs as BCRs, we find that residual splenic B cells arrest at distinct developmental stages, yet exhibit uniformly low BCR densities, elevated basal activation, and profoundly muted responses to BCR ligation and, when captured as hybridoma mAb lines, maintain their dual (gp41/lipid) affinities and capacities to neutralize HIV-1, establishing a key role for anergy in suppressing residual 2F5- or 4E10-expressing B cells. Importantly, serum IgGs from naive 2F5 and 4E10 KI strains selectively eliminate gp41 and lipid binding, respectively, suggesting B cells expressing 2F5 or 4E10 as BCRs exhibit specificity for a distinct spectrum of host Ags, including selective interactions by 2F5 BCR(+) B cells (i.e., and not 4E10 BCR(+) B cells) with those mimicked by its gp41 neutralization epitope.
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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.