{"doi":"10.1016/j.celrep.2020.03.038","title":"BCR-Induced Ca2+ Signals Dynamically Tune Survival, Metabolic Reprogramming, and Proliferation of Naive B Cells","abstract":"B cell receptor (BCR) engagement induces naive B cells to differentiate and perform critical immune-regulatory functions. Acquisition of functional specificity requires that a cell survive, enter the cell cycle, and proliferate. We establish that quantitatively distinct Ca 2+ signals triggered by variations in the extent of BCR engagement dynamically regulate these transitions by controlling nuclear factor κB (NF-κB), NFAT, and mTORC1 activity. Weak BCR engagement induces apoptosis by failing to activate NF-κB-driven anti-apoptotic gene expression. Stronger signals that trigger more robust Ca 2+ signals promote NF-κB-dependent survival and NFAT-, mTORC1-, and c-Myc-dependent cell-cycle entry and proliferation. Finally, we establish that CD40 or TLR9 costimulation circumvents these Ca 2+ -regulated checkpoints of B cell activation and proliferation. As altered BCR signaling is linked to autoimmunity and B cell malignancies, these results have important implications for understanding the pathogenesis of aberrant B cell activation and differentiation and therapeutic approaches to target these responses.","journal":"Cell Reports","year":2020,"id":58624,"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":71,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9452,"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":307543,"name":"Xiaohong Liu","orcid":"0000-0002-6803-5846","position":1,"is_corresponding":false},{"id":248116,"name":"Arpita Myles","orcid":null,"position":2,"is_corresponding":false},{"id":307544,"name":"Satabdi Nandi","orcid":"0000-0002-7693-952X","position":3,"is_corresponding":false},{"id":307545,"name":"Youhai H. Chen","orcid":"0000-0002-9695-6757","position":4,"is_corresponding":false},{"id":307546,"name":"Uri Hershberg","orcid":"0000-0002-6425-5980","position":5,"is_corresponding":false},{"id":239930,"name":"Igor E. Brodsky","orcid":"0000-0001-7970-872X","position":6,"is_corresponding":false},{"id":244598,"name":"Michael P. Cancro","orcid":"0000-0002-8659-3227","position":7,"is_corresponding":false},{"id":307547,"name":"Christopher J. Lengner","orcid":"0000-0002-0574-5189","position":8,"is_corresponding":false},{"id":242811,"name":"Michael J. May","orcid":"0000-0002-2485-3716","position":9,"is_corresponding":false},{"id":155472,"name":"Bruce D. Freedman","orcid":"0000-0003-4487-7210","position":10,"is_corresponding":false},{"id":307542,"name":"Corbett T. Berry","orcid":"0000-0001-9348-2034","position":0,"is_corresponding":true}],"reference_count":99,"raw_metadata":null,"created_at":"2026-07-18T21:07:33.416320Z","pmid":"32294437","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":[]}