{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T06:31:07Z","timestamp":1764570667227,"version":"3.46.0"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":54,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC3404304"],"award-info":[{"award-number":["2023YFC3404304"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2024AFB581"],"award-info":[{"award-number":["2024AFB581"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>CD40\u2010CD154 pathway inhibitors are considered indispensable immunosuppressive drugs in xenotransplantation. At present, novel anti\u2010CD154 and anti\u2010CD40 monoclonal antibodies (mAbs) are continuously being developed. It is important to establish a simple and efficient in vitro method to evaluate the effectiveness of these therapeutic mAbs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A modified CD40L\u2010activated B\u2010cell proliferation model was established using irradiated NIH\/3T3 cells transfected with human CD40 ligand (hCD40L\u2010NIH\/3T3) as stimulator cells and human or rhesus monkey peripheral blood mononuclear cells (PBMCs) as responder cells. After 8\u00a0days of culture, B\u2010cell proliferation was detected by flow cytometry. Various concentrations of anti\u2010CD40 or anti\u2010CD154 mAbs were added to the co\u2010culture system as an intervention. The inhibitory effects of anti\u2010CD154 and anti\u2010CD40 mAbs on the proliferation of B cells from humans and rhesus monkeys were studied and compared.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After 8\u00a0days of co\u2010culture, the proliferation rate of B cells in both human and rhesus monkey PBMCs was more than 80%, and the expression of MHC\u2010II and the co\u2010stimulatory molecules CD80, CD86, and CD40 on B cells was significantly up\u2010regulated. All three anti\u2010CD154 mAbs showed a similar strong inhibitory effect on human B\u2010cell proliferation, but the inhibitory effect on the proliferation of rhesus monkey B cells was weaker than that on human B cells, which showed a typical dose\u2010dependent inhibition. The three anti\u2010CD40 mAbs from different sources had different effects. One mAbs potently inhibited both human and monkey B\u2010cell proliferation, whereas the other two mAbs exhibited strong or moderate inhibitory effects on human B\u2010cell proliferation but had little inhibitory effect on monkey B\u2010cell proliferation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We have successfully established a modified CD40L\u2010activated B\u2010cell proliferation model for the in vitro evaluation of CD40\u2010CD154 pathway inhibitors, which may provide important evidence for the selection of appropriate therapeutic antibodies and their dose determination for xenotransplantation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/xen.70029","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T01:09:00Z","timestamp":1740532140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Modified CD40L\u2010Activated B\u2010Cell Proliferation Model for Validating the Suppressive Activity of CD40\u2010CD154 Pathway Inhibitors"],"prefix":"10.1111","volume":"32","author":[{"given":"Man","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Organ Transplantation Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences  Wuhan 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