{"doi":"10.1172/jci170118","title":"B cells mediate lung ischemia/reperfusion injury by recruiting classical monocytes via synergistic B cell receptor/TLR4 signaling","abstract":"Ischemia/reperfusion injury-mediated (IRI-mediated) primary graft dysfunction (PGD) adversely affects both short- and long-term outcomes after lung transplantation, a procedure that remains the only treatment option for patients suffering from end-stage respiratory failure. While B cells are known to regulate adaptive immune responses, their role in lung IRI is not well understood. Here, we demonstrated by intravital imaging that B cells are rapidly recruited to injured lungs, where they extravasate into the parenchyma. Using hilar clamping and transplant models, we observed that lung-infiltrating B cells produce the monocyte chemokine CCL7 in a TLR4-TRIF-dependent fashion, a critical step contributing to classical monocyte (CM) recruitment and subsequent neutrophil extravasation, resulting in worse lung function. We found that synergistic BCR-TLR4 activation on B cells is required for the recruitment of CMs to the injured lung. Finally, we corroborated our findings in reperfused human lungs, in which we observed a correlation between B cell infiltration and CM recruitment after transplantation. This study describes a role for B cells as critical orchestrators of lung IRI. As B cells can be depleted with currently available agents, our study provides a rationale for clinical trials investigating B cell-targeting therapies.","journal":"Journal of Clinical Investigation","year":2024,"id":424098,"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":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1078113,"name":"Yun Zhu Bai","orcid":"0000-0002-7290-6739","position":1,"is_corresponding":false},{"id":1096601,"name":"Yuhei Yokoyama","orcid":"0009-0004-4577-2554","position":2,"is_corresponding":false},{"id":773030,"name":"Deniz B. Morkan","orcid":null,"position":3,"is_corresponding":false},{"id":443821,"name":"Zhiyi Liu","orcid":"0000-0002-8122-8474","position":4,"is_corresponding":false},{"id":867739,"name":"Junedh Amrute","orcid":"0000-0002-6851-0168","position":5,"is_corresponding":false},{"id":1221025,"name":"Alejandro De Filippis Falcon","orcid":null,"position":6,"is_corresponding":false},{"id":376145,"name":"Yuriko Terada","orcid":"0000-0003-1598-9360","position":7,"is_corresponding":false},{"id":497620,"name":"Fuyi Liao","orcid":"0000-0001-7733-084X","position":8,"is_corresponding":false},{"id":376146,"name":"Wenjun Li","orcid":"0000-0002-1923-5016","position":9,"is_corresponding":false},{"id":676720,"name":"Hailey M. Shepherd","orcid":"0000-0001-6798-6415","position":10,"is_corresponding":false},{"id":288869,"name":"Ramsey R. Hachem","orcid":"0000-0002-0708-1937","position":11,"is_corresponding":false},{"id":376149,"name":"Varun Puri","orcid":"0000-0001-7761-8421","position":12,"is_corresponding":false},{"id":247530,"name":"Kory J. Lavine","orcid":"0000-0003-1948-9945","position":13,"is_corresponding":false},{"id":230331,"name":"Andrew E. Gelman","orcid":"0000-0002-0711-6343","position":14,"is_corresponding":false},{"id":232806,"name":"Ankit Bharat","orcid":"0000-0002-1248-0457","position":15,"is_corresponding":false},{"id":273856,"name":"Daniel Kreisel","orcid":"0000-0002-7711-8651","position":16,"is_corresponding":false},{"id":376148,"name":"Ruben G. Nava","orcid":"0000-0001-5685-9445","position":17,"is_corresponding":false},{"id":1221024,"name":"Khashayar Farahnak","orcid":null,"position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T01:58:07.191194Z","pmid":"38488011","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":[]}