{"doi":"10.1016/j.celrep.2024.115190","title":"IL-21 shapes the B cell response in a context-dependent manner","abstract":"The T-cell-derived cytokine IL-21 is crucial for germinal center (GC) responses, but its precise role in B cell function has remained elusive. Using IL-21 receptor ( Il21r ) conditional knockout mice and ex vivo culture systems, we demonstrate that IL-21 has dual effects on B cells. While IL-21 induced apoptosis in a STAT3-dependent manner in naive B cells, it promoted the robust proliferation of pre-activated B cells, particularly IgG1 + B cells. In vivo , B-cell-specific Il21r deletion impaired IgG1 responses post-immunization and disrupted progression from pre-GC to GC states. Although Il21r deficiency did not affect the proportion of IgG1 + cells among GC B cells, it greatly diminished the proportion of IgG1 + cells among the plasmablast/plasma cell population. Collectively, our findings suggest that IL-21 serves as a critical regulator of B cell fates, influencing B cell apoptosis and proliferation in a context-dependent manner. • IL-21 induces apoptosis in naive B cells but promotes proliferation in activated B cells • IL-21 promotes preferential expansion of IgG1 + B cells through synergy with BCR signaling • Il21r deletion in B cells leads to quantitative and qualitative defects in GC responses Kim et al. observed that IL-21 regulates B cell fate in a context-dependent manner. IL-21 induces apoptosis in naive B cells but promotes proliferation of activated B cells, especially IgG1 + cells. B-cell-specific IL-21 receptor deficiency impairs GC formation and IgG1 antibody production.","journal":"Cell Reports","year":2025,"id":510547,"datarank":0.5263824704827239,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0770226294496252,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0770226294496252,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":17,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE280837","GSE280838"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1367655,"name":"Francesca Manara","orcid":null,"position":1,"is_corresponding":false},{"id":322859,"name":"Simon Grassmann","orcid":"0000-0002-8336-3418","position":2,"is_corresponding":false},{"id":665550,"name":"Kalina T. Belcheva","orcid":null,"position":3,"is_corresponding":false},{"id":1367656,"name":"Kanelly Reyes","orcid":null,"position":4,"is_corresponding":false},{"id":636463,"name":"Hyunu Kim","orcid":"0000-0001-6452-8152","position":5,"is_corresponding":false},{"id":684662,"name":"Stephanie Downs‐Canner","orcid":"0000-0002-6870-3285","position":6,"is_corresponding":false},{"id":567654,"name":"William T. Yewdell","orcid":"0000-0002-5712-1896","position":7,"is_corresponding":false},{"id":61584,"name":"Joseph C. Sun","orcid":"0000-0001-8062-9033","position":8,"is_corresponding":false},{"id":415573,"name":"Jayanta Chaudhuri","orcid":"0000-0002-3838-0075","position":9,"is_corresponding":false},{"id":1022656,"name":"Youngjun Kim","orcid":"0000-0003-3346-9457","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:47:36.538276Z","pmid":"39792552","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":[]}