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Here we constructed a humanized (THX) mouse by grafting non-\u03b3-irradiated, genetically myeloablated\n                    <jats:italic>Kit<\/jats:italic>\n                    <jats:sup>W-41J<\/jats:sup>\n                    mutant immunodeficient pups with human cord blood CD34\n                    <jats:sup>+<\/jats:sup>\n                    cells, followed by 17\u03b2-estradiol conditioning to promote immune cell differentiation. THX mice reconstitute a human lymphoid and myeloid immune system, including marginal zone B cells, germinal center B cells, follicular helper T cells and neutrophils, and develop well-formed lymph nodes and intestinal lymphoid tissue, including Peyer\u2019s patches, and human thymic epithelial cells. These mice have diverse human B cell and T cell antigen receptor repertoires and can mount mature T cell-dependent and T cell-independent antibody responses, entailing somatic hypermutation, class-switch recombination, and plasma cell and memory B cell differentiation. Upon flagellin or a Pfizer-BioNTech coronavirus disease 2019 (COVID-19) mRNA vaccination, THX mice mount neutralizing antibody responses to\n                    <jats:italic>Salmonella<\/jats:italic>\n                    or severe acute respiratory syndrome coronavirus 2 Spike S1 receptor-binding domain, with blood incretion of human cytokines, including APRIL, BAFF, TGF-\u03b2, IL-4 and IFN-\u03b3, all at physiological levels. These mice can also develop lupus autoimmunity after pristane injection. By leveraging estrogen activity to support human immune cell differentiation and maturation of antibody responses, THX mice provide a platform to study the human immune system and to develop human vaccines and therapeutics.\n                  <\/jats:p>","DOI":"10.1038\/s41590-024-01880-3","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T06:07:29Z","timestamp":1719295649000},"page":"1489-1506","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses"],"prefix":"10.1038","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8930-5817","authenticated-orcid":false,"given":"Daniel P.","family":"Chupp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9052-557X","authenticated-orcid":false,"given":"Carlos E.","family":"Rivera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1044-5148","authenticated-orcid":false,"given":"Yulai","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6597-1105","authenticated-orcid":false,"given":"Yijiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2613-9364","authenticated-orcid":false,"given":"Patrick S.","family":"Ramsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5822-0570","authenticated-orcid":false,"given":"Zhenming","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8982-5177","authenticated-orcid":false,"given":"Paolo","family":"Casali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"key":"1880_CR1","first-page":"433","volume":"34","author":"J Zschaler","year":"2014","unstructured":"Zschaler, J., Schlorke, D. & Arnhold, J. 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