ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Rescue of HIV-1 broad neutralizing antibody-expressing B cells in 2F5 VH x VL knockin mice reveals multiple tolerance controls.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 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
- Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial.PLoS pathogens · 2017Trial
- 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
- An HIV-1 gp41 peptide-liposome vaccine elicits neutralizing epitope-targeted antibody responses in healthy individuals.medRxiv : the preprint server for health sciences · 2025Article
- 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
- Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions.Cell reports. Medicine · 2023Article
- An engineered HIV-1 Gag-based VLP displaying high antigen density induces strong antibody-dependent functional immune responses.NPJ vaccines · 2023Article
- B cells expressing IgM B cell receptors of HIV-1 neutralizing antibodies discriminate antigen affinities by sensing binding association rates.Cell reports · 2022Article
- Continuous Culture of Mouse Primary B Lymphocytes by Forced Expression ofJournal of immunology (Baltimore, Md. : 1950) · 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
- B Cells Carrying Antigen Receptors Against Microbes as Tools for Vaccine Discovery and Design.Current topics in microbiology and immunology · 2020Review
- Histone H2A-Reactive B Cells Are Functionally Anergic in Healthy Mice With Potential to Provide Humoral Protection Against HIV-1.Frontiers in immunology · 2020Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The HIV-1 broadly neutralizing Ab (bnAb) 2F5 has been shown to be poly-/self-reactive in vitro, and we previously demonstrated that targeted expression of its VDJ rearrangement alone was sufficient to trigger a profound B cell developmental blockade in 2F5 V(H) knockin (KI) mice, consistent with central deletion of 2F5 H chain-expressing B cells. In this study, we generate a strain expressing the entire 2F5 bnAb specificity, 2F5 V(H) × V(L) KI mice, and find an even higher degree of tolerance control than observed in the 2F5 V(H) KI strain. Although B cell development was severely impaired in 2F5 V(H) × V(L) KI animals, we demonstrate rescue of their B cells when cultured in IL-7/BAFF. Intriguingly, even under these conditions, most rescued B cell hybridomas produced mAbs that lacked HIV-1 Envelope (Env) reactivity due to editing of the 2F5 L chain, and the majority of rescued B cells retained an anergic phenotype. Thus, when clonal deletion is circumvented, κ editing and anergy are additional safeguards preventing 2F5 V(H)/V(L) expression by immature/transitional B cells. Importantly, 7% of rescued B cells retained 2F5 V(H)/V(L) expression and secreted Env-specific mAbs with HIV-1-neutralizing activity. This partial rescue was further corroborated in vivo, as reflected by the anergic phenotype of most rescued B cells in 2F5 V(H) × V(L) KI × Eμ-Bcl-2 transgenic mice and significant (yet modest) enrichment of Env-specific B cells and serum Igs. The rescued 2F5 mAb-producing B cell clones in this study are the first examples, to our knowledge, of in vivo-derived bone marrow precursors specifying HIV-1 bnAbs and provide a starting point for design of strategies aimed at rescuing such B cells.
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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.