{"doi":"10.1126/sciadv.ade8928","title":"Intrinsic B cell TLR-BCR linked coengagement induces class-switched, hypermutated, neutralizing antibody responses in absence of T cells","abstract":"Maturation of antibody responses entails somatic hypermutation (SHM), class-switch DNA recombination (CSR), plasma cell differentiation, and generation of memory B cells, and it is thought to require T cell help. We showed that B cell Toll-like receptor 4 (TLR4)–B cell receptor (BCR) (receptor for antigen) coengagement by 4-hydroxy-3-nitrophenyl acetyl (NP)–lipopolysaccharide (LPS) ( Escherichia coli lipid A polysaccharide O-antigen) or TLR5-BCR coengagement by Salmonella flagellin induces mature antibody responses to NP and flagellin in Tcr β −/− Tcr δ −/− and NSG/B mice. TLR-BCR coengagement required linkage of TLR and BCR ligands, “linked coengagement.” This induced B cell CSR/SHM, germinal center–like differentiation, clonal expansion, intraconal diversification, plasma cell differentiation, and an anamnestic antibody response. In Tcr β −/− Tcr δ −/− mice, linked coengagement of TLR4-BCR by LPS or TLR5-BCR by flagellin induced protective antibodies against E. coli or Salmonella Typhimurium. Our findings unveiled a critical role of B cell TLRs in inducing neutralizing antibody responses, including those to microbial pathogens, without T cell help.","journal":"Science Advances","year":2023,"id":332734,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9622,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1059368,"name":"Yulai Zhou","orcid":"0000-0002-1044-5148","position":1,"is_corresponding":false},{"id":379112,"name":"Daniel P. Chupp","orcid":"0000-0002-8930-5817","position":2,"is_corresponding":false},{"id":567341,"name":"Hui Yan","orcid":"0000-0002-6990-2526","position":3,"is_corresponding":false},{"id":486441,"name":"Amanda Fisher","orcid":"0000-0002-2634-144X","position":4,"is_corresponding":false},{"id":742246,"name":"Raphael Simon","orcid":"0000-0002-4136-0948","position":5,"is_corresponding":false},{"id":231705,"name":"Hong Zan","orcid":"0000-0002-2873-7034","position":6,"is_corresponding":false},{"id":379113,"name":"Zhenming Xu","orcid":"0000-0002-5822-0570","position":7,"is_corresponding":false},{"id":231706,"name":"Paolo Casali","orcid":"0000-0002-8982-5177","position":8,"is_corresponding":false},{"id":567345,"name":"Carlos Eduardo Rivera","orcid":"0000-0001-9052-557X","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":null,"created_at":"2026-07-19T01:09:35.125543Z","pmid":"37115935","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":[]}