ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Induction of HIV-1 broad neutralizing antibodies in 2F5 knock-in mice: selection against membrane proximal external region-associated autoreactivity limits T-dependent responses.
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 64 papers, 1 of them a synthesis that pooled it.
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
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- A systematic review of syphilis serological treatment outcomes in HIV-infected and HIV-uninfected persons: rethinking the significance of serological non-responsiveness and the serofast state after therapy.BMC infectious diseases · 2015Pooled it
- Vaccination induces HIV broadly neutralizing antibody precursors in humans.Science (New York, N.Y.) · 2022Trial
- 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
- Clonal dynamics of germinal center refueling by secondary immunization.bioRxiv : the preprint server for biology · 2026Article
- SARS-CoV-2 spike peptide analysis reveals a highly conserved region that elicits potentially pathogenic autoantibodies: implications to pan-coronavirus vaccine development.Frontiers in immunology · 2025Article
- Review
- Oral tolerance to systemic vaccination remains intact without RORγt expression in regulatory T cells.iScience · 2023Article
- An engineered HIV-1 Gag-based VLP displaying high antigen density induces strong antibody-dependent functional immune responses.NPJ vaccines · 2023Article
- Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies.Nature reviews. Immunology · 2023Review
- Editorial: Does selection against autoreactive B cells limit affinity maturation to pathogens?Frontiers in immunology · 2023Article
- B cells in the balance: Offsetting self-reactivity avoidance with protection against foreign.Frontiers in immunology · 2022Review
- Membrane Env Liposomes Facilitate Immunization with Multivalent Full-Length HIV Spikes.Journal of virology · 2021Article
- 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
- 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
- Identification of variant HIV envelope proteins with enhanced affinities for precursors to anti-gp41 broadly neutralizing antibodies.PloS one · 2019Article
- Structure of the membrane proximal external region of HIV-1 envelope glycoprotein.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Poly- and autoreactivity of HIV-1 bNAbs: implications for vaccine design.Retrovirology · 2018Review
- Immune Correlate-Guided HIV Vaccine Design.Cell host & microbe · 2018Review
4 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
14 authors at 2 institutions in 1 country.
Funding
Abstract
A goal of HIV-1 vaccine development is to elicit broadly neutralizing Abs (BnAbs). Using a knock-in (KI) model of 2F5, a human HIV-1 gp41 membrane proximal external region (MPER)-specific BnAb, we previously demonstrated that a key obstacle to BnAb induction is clonal deletion of BnAb-expressing B cells. In this study of this model, we provide a proof-of-principle that robust serum neutralizing IgG responses can be induced from pre-existing, residual, self-reactive BnAb-expressing B cells in vivo using a structurally compatible gp41 MPER immunogen. Furthermore, in CD40L-deficient 2F5 KI mice, we demonstrate that these BnAb responses are elicited via a type II T-independent pathway, coinciding with expansion and activation of transitional splenic B cells specific for 2F5's nominal gp41 MPER-binding epitope (containing the 2F5 neutralization domain ELDKWA). In contrast, constitutive production of nonneutralizing serum IgGs in 2F5 KI mice is T dependent and originates from a subset of splenic mature B2 cells that have lost their ability to bind 2F5's gp41 MPER epitope. These results suggest that residual, mature B cells expressing autoreactive BnAbs, like 2F5 as BCR, may be limited in their ability to participate in T-dependent responses by purifying selection that selectively eliminates reactivity for neutralization epitope-containing/mimicked host Ags.
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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.