{"doi":"10.1101/2023.07.23.550231","title":"Mechanotransduction governs CD40 function and underlies X-linked Hyper IgM syndrome","abstract":"B cell maturation in germinal centers (GCs) depends on cognate interactions between the T and B cells. Upon interaction with CD40 ligand (CD40L) on T cells, CD40 delivers co-stimulatory signals alongside B cell antigen receptor (BCR) signaling to regulate affinity maturation and antibody class-switch during GC reaction. Mutations in CD40L disrupt interactions with CD40, which lead to abnormal antibody responses in immune deficiencies known as X-linked Hyper IgM syndrome (X-HIgM). Assuming that physical interactions between highly mobile T and B cells generate mechanical forces on CD40-CD40L bonds, we set out to study the B cell mechanobiology mediated by CD40-CD40L interaction. Using a suite of biophysical assays we find that CD40 forms catch bond with CD40L where the bond lasts longer at larger forces, B cells exert tension on CD40-CD40L bonds, and force enhances CD40 signaling and antibody class-switch. Significantly, X-HIgM CD40L mutations impair catch bond formation, suppress endogenous tension, and reduce force-enhanced CD40 signaling, leading to deficiencies in antibody class switch. Our findings highlight the critical role of mechanotransduction in CD40 function and provide insights into the molecular mechanisms underlying X-HIgM syndrome.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":393486,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"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":336860,"name":"Stefano Travaglino","orcid":"0000-0002-7362-2527","position":1,"is_corresponding":false},{"id":1167554,"name":"Matthias Münchhalfen","orcid":"0000-0002-9240-9342","position":2,"is_corresponding":false},{"id":1167555,"name":"Richard Görg","orcid":"0000-0003-4513-8698","position":3,"is_corresponding":false},{"id":1031970,"name":"Zhe Zhong","orcid":"0009-0004-1125-4441","position":4,"is_corresponding":false},{"id":643803,"name":"Jintian Lyu","orcid":null,"position":5,"is_corresponding":false},{"id":1167556,"name":"David M. Reyes-Aguilar","orcid":"0009-0006-0426-526X","position":6,"is_corresponding":false},{"id":1167557,"name":"Jürgen Wienands","orcid":"0000-0001-8278-7668","position":7,"is_corresponding":false},{"id":254092,"name":"Ankur Singh","orcid":"0000-0002-3501-2277","position":8,"is_corresponding":false},{"id":336861,"name":"Cheng Zhu","orcid":"0000-0002-1718-565X","position":9,"is_corresponding":false},{"id":823615,"name":"Hyun-Kyu Choi","orcid":"0000-0001-9192-891X","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-19T01:19:05.913428Z","pmid":"37546834","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":[]}