{"doi":"10.1101/2024.02.05.578789","title":"Preservation of memory B cell homeostasis in an individual producing broadly neutralising antibodies against HIV-1","abstract":"Abstract Immunological determinants favouring emergence of broadly neutralising antibodies are crucial to the development of HIV-1 vaccination strategies. Here, we combined RNAseq and B cell cloning approaches to isolate a broadly neutralising antibody (bnAb) ELC07 from an individual living with untreated HIV-1. Using single particle cryogenic electron microscopy (cryo-EM), we show that the antibody recognises a conformational epitope at the gp120-gp41 interface. ELC07 binds the closed state of the viral glycoprotein causing considerable perturbations to the gp41 trimer core structure. Phenotypic analysis of memory B cell subsets from the ELC07 bnAb donor revealed a lack of expected HIV-1-associated dysfunction, specifically no increase in CD21 - /CD27 - cells was observed whilst the resting memory (CD21 + /CD27 + ) population appeared preserved despite uncontrolled HIV-1 viraemia. Moreover, single cell transcriptomes of memory B cells from this bnAb donor showed a resting memory phenotype irrespective of the epitope they targeted or their ability to neutralise diverse strains of HIV-1. Strikingly, single memory B cells from the ELC07 bnAb donor were transcriptionally similar to memory B cells from HIV-negative individuals. Our results demonstrate that potent bnAbs can arise without the HIV-1-induced dysregulation of the memory B cell compartment and suggest that sufficient levels of antigenic stimulation with a strategically designed immunogen could be effective in HIV-negative vaccine recipients.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":489938,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9485,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":621318,"name":"Luke Muir","orcid":"0000-0002-7834-6066","position":1,"is_corresponding":false},{"id":235858,"name":"Ondřej Suchánek","orcid":"0000-0003-1048-5251","position":2,"is_corresponding":false},{"id":1335280,"name":"Joshua Hope","orcid":"0000-0003-2742-5538","position":3,"is_corresponding":false},{"id":1066692,"name":"Corinna Pade","orcid":"0000-0003-0626-2346","position":4,"is_corresponding":false},{"id":991133,"name":"Joseph M. 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Gupta","orcid":"0000-0001-9751-1808","position":17,"is_corresponding":false},{"id":270800,"name":"Katie J. Doores","orcid":"0000-0002-5507-1725","position":18,"is_corresponding":false},{"id":277729,"name":"Peter Cherepanov","orcid":"0000-0002-0634-538X","position":19,"is_corresponding":false},{"id":991135,"name":"Áine McKnight","orcid":"0000-0002-8113-817X","position":20,"is_corresponding":false},{"id":15662,"name":"Menna R. Clatworthy","orcid":"0000-0002-3340-9828","position":21,"is_corresponding":false},{"id":270794,"name":"Laura E. 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