{"doi":"10.1126/sciimmunol.add1823","title":"IL-21R signal reprogramming cooperates with CD40 and BCR signals to select and differentiate germinal center B cells","abstract":"Both B cell receptor (BCR) and CD40 signaling are rewired in germinal center (GC) B cells (GCBCs) to synergistically induce c-MYC and phosphorylated S6 ribosomal protein (p-S6), markers of positive selection. How interleukin-21 (IL-21), a key T follicular helper (T FH )–derived cytokine, affects GCBCs is unclear. Like BCR and CD40 signals, IL-21 receptor (IL-21R) plus CD40 signals also synergize to induce c-MYC and p-S6 in GCBCs. However, IL-21R plus CD40 stimulation differentially affects GCBC fate compared with BCR plus CD40 ligation—engaging unique molecular mechanisms—as revealed by bulk RNA sequencing (RNA-seq), single-cell RNA-seq, and flow cytometry of GCBCs in vitro and in vivo. Whereas both signal pairs induced BLIMP1 in some GCBCs, only the IL-21R/CD40 combination induced IRF4 hi /CD138 + cells, indicative of plasma cell differentiation, along with CCR6 + /CD38 + memory B cell precursors. These findings reveal a second positive selection pathway in GCBCs, document rewired IL-21R signaling in GCBCs, and link specific T FH - and Ag-derived signals to GCBC differentiation.","journal":"Science Immunology","year":2023,"id":317311,"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":80,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"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":237074,"name":"Laura Conter","orcid":"0000-0002-8528-0528","position":1,"is_corresponding":false},{"id":237069,"name":"Rebecca A. Elsner","orcid":"0000-0001-5364-8060","position":2,"is_corresponding":false},{"id":237073,"name":"Shuchi Smita","orcid":"0000-0001-9276-8145","position":3,"is_corresponding":false},{"id":237067,"name":"Florian Weisel","orcid":"0000-0002-8679-9241","position":4,"is_corresponding":false},{"id":858336,"name":"Derrick Callahan","orcid":null,"position":5,"is_corresponding":false},{"id":1023459,"name":"Shuxian Wu","orcid":null,"position":6,"is_corresponding":false},{"id":3026,"name":"Maria Chikina","orcid":"0000-0003-2550-5403","position":7,"is_corresponding":false},{"id":237080,"name":"Mark J. Shlomchik","orcid":"0000-0002-2152-0959","position":8,"is_corresponding":false},{"id":237071,"name":"Wei Luo","orcid":"0000-0003-2826-1723","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T01:06:50.336418Z","pmid":"36800413","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":[]}