{"doi":"10.1172/jci186258","title":"Multiomic analysis reveals a key BCAT1 role in mTOR activation by B cell receptor and TLR9","abstract":"B lymphocytes play major adaptive immune roles, producing antibodies and driving T cell responses. However, how immunometabolism networks support B cell activation and differentiation in response to distinct receptor stimuli remains incompletely understood. To gain insights, we systematically investigated acute primary human B cell transcriptional, translational, and metabolomic responses to B cell receptor (BCR), TLR9, CD40-ligand (CD40L), IL-4, or combinations thereof. T cell-independent BCR/TLR9 costimulation, which drives malignant and autoimmune B cell states, highly induced transaminase branched chain amino acid transaminase 1 (BCAT1), which localized to lysosomal membranes to support branched chain amino acid synthesis and mTORC1 activation. BCAT1 inhibition blunted BCR/TLR9, but not CD40L/IL-4-triggered B cell proliferation, IL-10 expression, and BCR/TLR pathway-driven lymphoma xenograft outgrowth. These results provide a valuable resource, reveal receptor-mediated immunometabolism remodeling to support key B cell phenotypes, and identify BCAT1 as an activated B cell therapeutic target.","journal":"Journal of Clinical Investigation","year":2025,"id":522020,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"is_data_producer":false,"deposit_databanks":null,"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":1090719,"name":"Yizhe Sun","orcid":"0000-0002-5986-3826","position":1,"is_corresponding":false},{"id":1333189,"name":"Matthew Lim","orcid":"0000-0001-7347-8409","position":2,"is_corresponding":false},{"id":105021,"name":"Hardik Shah","orcid":"0000-0001-8408-5686","position":3,"is_corresponding":false},{"id":1393447,"name":"Joao A Paulo","orcid":null,"position":4,"is_corresponding":false},{"id":1392931,"name":"R.G. Ahmed","orcid":"0000-0001-5644-8291","position":5,"is_corresponding":false},{"id":1392932,"name":"Weixing Li","orcid":"0000-0002-1697-7444","position":6,"is_corresponding":false},{"id":916716,"name":"Yuchen Zhang","orcid":"0000-0001-8944-5230","position":7,"is_corresponding":false},{"id":255857,"name":"Haopeng Yang","orcid":"0000-0002-3870-2679","position":8,"is_corresponding":false},{"id":1333190,"name":"Liang Wei Wang","orcid":"0000-0002-0324-8744","position":9,"is_corresponding":false},{"id":1103304,"name":"Daniel Strebinger","orcid":"0000-0001-8732-6414","position":10,"is_corresponding":false},{"id":415450,"name":"Nicholas A. Smith","orcid":"0000-0001-8894-4249","position":11,"is_corresponding":false},{"id":1392933,"name":"Meng Li","orcid":"0000-0002-6184-8887","position":12,"is_corresponding":false},{"id":1332719,"name":"Merrin Man‐Long Leong","orcid":"0000-0003-4753-2285","position":13,"is_corresponding":false},{"id":855592,"name":"Michael Lutchenkov","orcid":null,"position":14,"is_corresponding":false},{"id":813974,"name":"Jin‐Hua Liang","orcid":null,"position":15,"is_corresponding":false},{"id":854877,"name":"Zhi‐Xuan Li","orcid":"0000-0002-8590-875X","position":16,"is_corresponding":false},{"id":519229,"name":"Yin Wang","orcid":"0000-0002-8137-7496","position":17,"is_corresponding":false},{"id":267781,"name":"Rishi Puri","orcid":"0000-0001-8849-7426","position":18,"is_corresponding":false},{"id":237422,"name":"Ari Melnick","orcid":"0000-0002-8074-2287","position":19,"is_corresponding":false},{"id":17225,"name":"Michael R. Green","orcid":"0000-0001-6309-9472","position":20,"is_corresponding":false},{"id":3257,"name":"John M. Asara","orcid":"0000-0001-7450-2589","position":21,"is_corresponding":false},{"id":1333541,"name":"Adonia E. Papathanassiu","orcid":null,"position":22,"is_corresponding":false},{"id":106756,"name":"Duane R. Wesemann","orcid":"0000-0002-6690-944X","position":23,"is_corresponding":false},{"id":107041,"name":"Steven P. Gygi","orcid":"0000-0001-7626-0034","position":24,"is_corresponding":false},{"id":31806,"name":"Vamsi K. Mootha","orcid":"0000-0001-9924-642X","position":25,"is_corresponding":false},{"id":99042,"name":"Benjamin E. Gewurz","orcid":"0000-0002-3965-3418","position":26,"is_corresponding":false},{"id":1392930,"name":"Rui Guo","orcid":"0000-0001-7417-7018","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-19T02:49:49.198144Z","pmid":"40924473","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":[]}