{"doi":"10.1172/jci140590","title":"Early T follicular helper cell activity accelerates hepatitis C virus-specific B cell expansion","abstract":"Early appearance of neutralizing antibodies during acute hepatitis C virus (HCV) infection is associated with spontaneous viral clearance. However, the longitudinal changes in antigen-specific memory B cell (MBCs) associated with divergent HCV infection outcomes remain undefined. We characterized longitudinal changes in E2 glycoprotein-specific MBCs from subjects who either spontaneously resolved acute HCV infection or progressed to chronic infection, using single-cell RNA-seq and functional assays. HCV-specific antibodies in plasma from chronically infected subjects recognized multiple E2 genotypes, while those from spontaneous resolvers exhibited variable cross-reactivity to heterotypic E2. E2-specific MBCs from spontaneous resolvers peaked early after infection (4-6 months), following expansion of activated circulating T follicular helper cells (cTfh) expressing interleukin 21. In contrast, E2-specific MBCs from chronically infected subjects, enriched in VH1-69, expanded during persistent infection (> 1 year), in the absence of significantly activated cTfh expansion. Early E2-specific MBCs from spontaneous resolvers produced monoclonal antibodies (mAbs) with fewer somatic hypermutations and lower E2 binding but similar neutralization as mAbs from late E2-specific MBCs of chronically infected subjects. These findings indicate that early cTfh activity accelerates expansion of E2-specific MBCs during acute infection, which might contribute to spontaneous clearance of HCV.","journal":"Journal of Clinical Investigation","year":2021,"id":186295,"datarank":0.7620008193987515,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.29167668700937904,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.29167668700937904,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":12,"citers_with_citation_signal":12,"citers_with_endowment":12,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01436357"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":743713,"name":"Maude Boisvert","orcid":"0000-0001-9304-7796","position":1,"is_corresponding":false},{"id":106175,"name":"Amit A. Upadhyay","orcid":"0000-0002-0952-4164","position":2,"is_corresponding":false},{"id":743714,"name":"Nathalie Bédard","orcid":"0000-0003-1043-8826","position":3,"is_corresponding":false},{"id":381611,"name":"Sydney A. Nelson","orcid":"0000-0001-8632-4855","position":4,"is_corresponding":false},{"id":743715,"name":"Julie Bruneau","orcid":"0000-0001-5519-8489","position":5,"is_corresponding":false},{"id":247224,"name":"Cynthia A. Derdeyn","orcid":"0000-0002-1220-513X","position":6,"is_corresponding":false},{"id":647696,"name":"Joseph Marcotrigiano","orcid":"0000-0001-7670-7836","position":7,"is_corresponding":false},{"id":305641,"name":"Matthew J. Evans","orcid":"0000-0002-4991-3877","position":8,"is_corresponding":false},{"id":232942,"name":"Steven E. Bosinger","orcid":"0000-0002-2116-5061","position":9,"is_corresponding":false},{"id":636807,"name":"Naglaa H. Shoukry","orcid":"0000-0002-8817-8238","position":10,"is_corresponding":false},{"id":227332,"name":"Arash Grakoui","orcid":"0000-0002-6002-7518","position":11,"is_corresponding":false},{"id":328827,"name":"Eduardo Salinas","orcid":"0000-0002-4490-9289","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T23:48:42.632147Z","pmid":"33463551","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":[]}