{"doi":"10.1101/2020.02.24.963629","title":"B cells expressing authentic naive human VRC01-class BCRs can be primed and recruited to germinal centers in multiple independent mouse models","abstract":"ABSTRACT Animal models of human antigen-specific B cell receptors (BCR) generally depend on “inferred germline” sequences, and thus their relationship to authentic naive human B cell BCR sequences and affinities is unclear. Here, BCR sequences from authentic naive human VRC01-class B cells from healthy human donors were selected for the generation of three new BCR knock-in mice. The BCRs span the physiological range of affinities found in humans, and use three different light chains (VK3-20, VK1-5, and VK1-33) found among subclasses of naive human VRC01-class B cells and HIV broadly neutralizing antibodies (bnAbs). The germline-targeting HIV immunogen eOD-GT8 60mer is currently in clinical trial as a candidate bnAb vaccine priming immunogen. To attempt to model human immune responses to the eOD-GT8 60mer, we tested each authentic naive human VRC01-class BCR mouse model under rare human physiological B cell precursor frequency conditions. B cells with high (HuGL18 HL ) or medium (HuGL17 HL ) affinity BCRs were primed, recruited to germinal centers, accrued substantial somatic hypermutation, and formed memory B cells. Precursor frequency and affinity interdependently influenced responses. Taken together, these experiments utilizing authentic naive human VRC01-class BCRs validate a central tenet of germline-targeting vaccine design and extend the overall concept of the reverse vaccinology approach to vaccine development.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":121501,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9288,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":236272,"name":"Robert Abbott","orcid":"0000-0003-0335-1175","position":1,"is_corresponding":false},{"id":217933,"name":"Colin Havenar‐Daughton","orcid":"0000-0002-2880-3927","position":2,"is_corresponding":false},{"id":560980,"name":"Patrick Skog","orcid":"0000-0002-5759-5071","position":3,"is_corresponding":false},{"id":561440,"name":"Rita Al-Kolla","orcid":null,"position":4,"is_corresponding":false},{"id":236275,"name":"Bettina Gröschel","orcid":"0000-0003-3127-5448","position":5,"is_corresponding":false},{"id":296040,"name":"Tanya R. Blane","orcid":"0000-0001-8132-3167","position":6,"is_corresponding":false},{"id":236277,"name":"Sergey Menis","orcid":"0000-0002-2487-5413","position":7,"is_corresponding":false},{"id":297046,"name":"Jenny Tuyet Tran","orcid":null,"position":8,"is_corresponding":false},{"id":561441,"name":"Theresa C. Thinnes","orcid":null,"position":9,"is_corresponding":false},{"id":560981,"name":"Sabrina A. Volpi","orcid":"0000-0002-3116-3465","position":10,"is_corresponding":false},{"id":561442,"name":"Mark Pintea","orcid":null,"position":11,"is_corresponding":false},{"id":109547,"name":"James E. Voss","orcid":"0000-0002-4777-1596","position":12,"is_corresponding":false},{"id":560982,"name":"Nicole Phelps","orcid":"0000-0001-9613-3921","position":13,"is_corresponding":false},{"id":560983,"name":"Ryan Tingle","orcid":"0000-0003-2874-7010","position":14,"is_corresponding":false},{"id":561443,"name":"Alberto R. Rodriguez","orcid":null,"position":15,"is_corresponding":false},{"id":560984,"name":"Greg Martin","orcid":"0000-0003-4647-8627","position":16,"is_corresponding":false},{"id":561444,"name":"Sergey Kupryianov","orcid":null,"position":17,"is_corresponding":false},{"id":236279,"name":"William R. Schief","orcid":"0000-0002-1120-0150","position":18,"is_corresponding":false},{"id":109546,"name":"David Nemazee","orcid":"0000-0002-4769-6311","position":19,"is_corresponding":false},{"id":103780,"name":"Shane Crotty","orcid":"0000-0002-6484-6262","position":20,"is_corresponding":false},{"id":108972,"name":"Deli Huang","orcid":"0000-0002-6989-639X","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T23:14:42.734024Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}