{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:20:59Z","timestamp":1792092059706,"version":"4.4.0"},"reference-count":80,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Porcine\u2010to\u2010human islet xenotransplantation offers a promising solution to type 1 diabetes. This study investigates the use of Belimumab, a human monoclonal antibody that inhibits B cell activating factor (BAFF) as part of an immunosuppressive regimen in porcine\u2010to\u2010non\u2010human primate xenotransplantation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Porcine islets were transplanted into Rhesus monkeys with an immunosuppressant regimen. Blood samples were collected from the monkeys pre\u2010 and post\u2010treatment, and single\u2010cell RNA sequencing was performed to investigate immune cell landscape changes, focusing on B cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      UMAP clustering of B cells identified five distinct subsets. Notably, Belimumab treatment significantly reduced the proportion of both CXCR5\n                      <jats:sup>+<\/jats:sup>\n                      and CXCR5\n                      <jats:sup>\u2212<\/jats:sup>\n                      atypical memory B cells, which possess the potential to differentiate into antibody\u2010secreting cells. Furthermore, differentially expressed gene (DEG) analysis revealed a comprehensive functional impairment, along with significant downregulation of activation markers such as CD69 and CD83, across all B cell subsets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study elucidates the mechanism of action of Belimumab in non\u2010human primate models, serving as preclinical subjects for B\u2010cell\u2013targeted therapy research in a xenotransplantation context. Significantly, our data indicate that Belimumab not only reduces the proportion of antibody\u2010secreting atypical memory B cells but also induces functional impairment across all B cell subsets. Given the potential pathogenic roles of atypical memory B cells in autoimmunity and other related settings, their reduction by Belimumab could play a crucial role in regulating B\u2010cell\u2013mediated immune responses in pig\u2010to\u2010non\u2010human primate pancreatic islet xenotransplantation. Thus, our findings highlight the prospective utility of Belimumab as a B cell suppressant in future clinical xenotransplantation applications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/xen.70076","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T09:16:11Z","timestamp":1758186971000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Single\u2010Cell RNA Analysis Reveals Reduced Frequency and Activity of CXCR5\n                    <sup>+<\/sup>\n                    Atypical Memory B Cells in Islet Xenotransplantation Treated With Clinically Applicable Immunosuppressants Including Belimumab"],"prefix":"10.1111","volume":"32","author":[{"given":"Yuji","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology College of Medicine Seoul National University  Seoul South Korea"},{"name":"Department of Biomedical Sciences College of Medicine Seoul National University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hwan","family":"Moon","sequence":"additional","affiliation":[{"name":"Samsung Genome Institute Samsung Medical Center  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Je","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology College of Medicine Seoul National University  Seoul South Korea"},{"name":"Department of Biomedical Sciences College of Medicine Seoul National University  Seoul South Korea"},{"name":"Transplantation Research Institute Seoul National University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daesik","family":"Kim","sequence":"additional","affiliation":[{"name":"Transplantation Research Institute Seoul National University  Seoul South Korea"},{"name":"PB Immune Therapeutics Inc  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Transplantation Research Institute Seoul National University  Seoul South Korea"},{"name":"PB Immune Therapeutics Inc  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong\u2010Min","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology College of Medicine Seoul National University  Seoul South Korea"},{"name":"Transplantation Research Institute Seoul National University  Seoul South Korea"},{"name":"Xenotransplantation Research Center College of Medicine Seoul National University  Seoul South Korea"},{"name":"Cancer Research Institute College of Medicine Seoul National University  Seoul South Korea"},{"name":"Department of Animal Health College of Health and Medical Sciences, Cheongju University  Cheongju South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung\u2010Gyu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology College of Medicine Seoul National University  Seoul South Korea"},{"name":"Department of Biomedical Sciences College of Medicine Seoul National University  Seoul South Korea"},{"name":"Transplantation Research Institute Seoul National University  Seoul South Korea"},{"name":"Xenotransplantation Research Center College of Medicine Seoul National University  Seoul South Korea"},{"name":"Cancer Research Institute College of Medicine Seoul National University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109119"},{"key":"e_1_2_9_3_1","unstructured":"International Diabetes Federation.2023.IDF Diabetes Atlas (11th ed.). 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