{"doi":"10.1111/xen.12691","title":"Mixed xenogeneic porcine chimerism tolerizes human anti‐pig natural antibody‐producing cells in a humanized mouse model","abstract":"BACKGROUND: A major obstacle to the success of organ transplantation from pigs to humans, necessitated by the shortage of human organs, is robust humoral immune rejection by pig-reactive human antibodies. Mixed xenogeneic hematopoietic chimerism induces xenoreactive B cell tolerance in rodents, but whether mixed pig/human chimerism could induce tolerance of human B cells to pig xenoantigens is unknown. METHODS: We investigated this question using a humanized mouse model in which durable mixed (pig-human) xenogeneic chimerism can be established. RESULTS: Human natural anti-pig cytotoxic antibodies, predominantly IgM, are detectable in non-chimeric humanized mouse serum, and pig-reactive antibodies were reduced in mixed chimeric versus non-chimeric humanized mice. This difference required persistent mixed chimerism and was not due to the adsorption of antibodies on pig cells in vivo. Furthermore, human B cells from spleens of mixed chimeric mice produced lower levels of anti-pig antibodies when stimulated in vitro compared with those from non-chimeric mice. CONCLUSIONS: Our findings demonstrate that mixed chimerism reduces human natural antibodies to pig xenoantigens, providing the first in vivo evidence of human B cell tolerance induction by mixed xenogeneic chimerism and supporting further evaluation of this approach for inducing human B cell tolerance to xenografts.","journal":"Xenotransplantation","year":2021,"id":199080,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":369806,"name":"Mohsen Khosravi‐Maharlooei","orcid":"0000-0002-1394-9245","position":1,"is_corresponding":false},{"id":774955,"name":"Andrea Vecchione","orcid":"0000-0002-5497-6856","position":2,"is_corresponding":false},{"id":774956,"name":"Steven Shao","orcid":"0000-0002-1963-5976","position":3,"is_corresponding":false},{"id":455016,"name":"Paresh Vishwasrao","orcid":"0000-0003-1775-9454","position":4,"is_corresponding":false},{"id":709819,"name":"Markus A. Hölzl","orcid":"0000-0002-3333-7967","position":5,"is_corresponding":false},{"id":677330,"name":"Kristjana Frangaj","orcid":"0009-0008-3723-574X","position":6,"is_corresponding":false},{"id":369810,"name":"Megan Sykes","orcid":"0000-0002-4947-4376","position":7,"is_corresponding":false},{"id":236117,"name":"Hao Wei Li","orcid":"0009-0005-2894-0293","position":8,"is_corresponding":false},{"id":677331,"name":"Elizabeth Waffarn","orcid":"0000-0001-5484-7344","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:50:36.595945Z","pmid":"33904221","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":[]}