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• W3158052169 abstract "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.We investigated this question using a humanized mouse model in which durable mixed (pig-human) xenogeneic chimerism can be established.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.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." @default.
• W3158052169 created "2021-05-10" @default.
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• W3158052169 date "2021-04-26" @default.
• W3158052169 modified "2023-10-18" @default.
• W3158052169 title "Mixed xenogeneic porcine chimerism tolerizes human anti‐pig natural antibody‐producing cells in a humanized mouse model" @default.
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• W3158052169 doi "https://doi.org/10.1111/xen.12691" @default.
• W3158052169 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8376778" @default.
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• W3158052169 hasPublicationYear "2021" @default.
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