{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:54:09Z","timestamp":1789912449745,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100018688","name":"Korea Disease Control and Prevention Agency","doi-asserted-by":"publisher","award":["2022\u2010ER1701\u201000"],"award-info":[{"award-number":["2022\u2010ER1701\u201000"]}],"id":[{"id":"10.13039\/100018688","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018688","name":"Korea Disease Control and Prevention Agency","doi-asserted-by":"publisher","award":["2022\u2010NI\u2010041\u201002"],"award-info":[{"award-number":["2022\u2010NI\u2010041\u201002"]}],"id":[{"id":"10.13039\/100018688","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018688","name":"Korea Disease Control and Prevention Agency","doi-asserted-by":"publisher","award":["2024\u2010ER1702\u201000"],"award-info":[{"award-number":["2024\u2010ER1702\u201000"]}],"id":[{"id":"10.13039\/100018688","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018688","name":"Korea Disease Control and Prevention Agency","doi-asserted-by":"publisher","award":["2025\u2010NI\u2010014\u201000"],"award-info":[{"award-number":["2025\u2010NI\u2010014\u201000"]}],"id":[{"id":"10.13039\/100018688","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Humanized mouse models are essential for studying the human immune response and antibody development. However, conventional models show limited B cell maturation and antigen\u2010specific humoral responses. To overcome these limitations, we used the NOG\u2010EXL mice expressing human interleukin 3 (IL\u20103)\u00a0and granulocyte\u2010macrophage colony\u2010stimulating factor (GM\u2010CSF)\u00a0to enhance myeloid and B\u2010cell lineage differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Human CD34\n                      <jats:sup>+<\/jats:sup>\n                      hematopoietic stem cells (HSC) were transplanted into NOG\u2010EXL mice to produce humanized immune systems. After immune cell reconstitution was confirmed across 12\u2009weeks, the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus (SFTSV) antigens. Peripheral blood mononuclear cells\u00a0and splenocytes\u00a0were analyzed using multicolor flow cytometry to assess human immune cell subsets. Antigen\u2010specific immunoglobulin G (IgG) production was quantified using enzyme\u2010linked immunosorbent assay (ELISA), and virus\u2010specific B cells were isolated using antigen\u2010labeled recombinant protein probes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twelve weeks after transplantation of HSCs into NOG\u2010EXL mice, they exhibited robust engraftment of human leukocytes, including T, B, and dendritic cells, compared to NOG mice. Unlike NOG mice, humanized NOG\u2010EXL mice exhibited an increase in human IgG levels, indicating the production of human antibody responses to antigens. Humanized NOG\u2010EXL mice were immunized twice every 2\u2009weeks with inactivated SFTSV, and antigen\u2010specific human antibodies against the virus were detected in the mouse sera by ELISA. Sera from SFTSV\u2010immunized humanized mice demonstrated neutralizing activity against SFTSV, confirming the induction of functional virus\u2010specific neutralizing antibodies. Antigen\u2010binding IgG\u2010positive human B cells were isolated from mouse splenocytes using recombinant protein probes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high\u2010affinity human monoclonal antibodies without genetic engineering.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70140","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T09:37:03Z","timestamp":1772962623000},"page":"378-388","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A humanized\n                    <scp>NOG<\/scp>\n                    \u2010\n                    <scp>EXL<\/scp>\n                    mouse model for producing severe fever with thrombocytopenia syndrome virus\u2013reactive human antibodies"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4703-4222","authenticated-orcid":false,"given":"Dong Hoon","family":"Lee","sequence":"first","affiliation":[{"name":"Division of Acute Viral Diseases Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health  Cheongju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyeong","family":"Bae","sequence":"additional","affiliation":[{"name":"Experimental Evaluation Department Non\u2010Clinical Evaluation Center, OSONG Medical Innovation Foundation (KBIOHealth)  Cheongju Korea"},{"name":"College of Pharmacy and Medical Research Center Chungbuk National University  Cheongju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumi","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Acute Viral Diseases Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health  Cheongju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Young","family":"Song","sequence":"additional","affiliation":[{"name":"Experimental Evaluation Department Non\u2010Clinical Evaluation Center, OSONG Medical Innovation Foundation (KBIOHealth)  Cheongju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Hyu","family":"Shin","sequence":"additional","affiliation":[{"name":"Experimental Evaluation Department Non\u2010Clinical Evaluation Center, OSONG Medical Innovation Foundation (KBIOHealth)  Cheongju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Experimental Evaluation Department Non\u2010Clinical Evaluation Center, OSONG Medical Innovation Foundation (KBIOHealth)  Cheongju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Ho","family":"Jang","sequence":"additional","affiliation":[{"name":"Experimental Evaluation Department Non\u2010Clinical Evaluation Center, OSONG Medical Innovation Foundation (KBIOHealth)  Cheongju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young\u2010sun","family":"Yun","sequence":"additional","affiliation":[{"name":"Division of Acute Viral Diseases Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health  Cheongju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010sook","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Acute Viral Diseases Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health  Cheongju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyuk","family":"Chu","sequence":"additional","affiliation":[{"name":"Division of Acute Viral Diseases Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health  Cheongju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jang\u2010Hoon","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Acute Viral Diseases Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health  Cheongju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Woo","family":"Kim","sequence":"additional","affiliation":[{"name":"Experimental Evaluation Department Non\u2010Clinical Evaluation Center, OSONG Medical Innovation Foundation (KBIOHealth)  Cheongju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2024.105820"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkad076"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105556"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2017"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2858"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.619236"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26045"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013137"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.29111"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-04-709584"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001374"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2018.09.005"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.142.6.1950"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.148.2.491"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203543"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.06192-11"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanwpc.2024.101133"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005893"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007375"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13061120"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3791\/52830"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00038"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00580"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.168.3.853"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.818814"}],"container-title":["Animal Models and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ame2.70140","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ame2.70140","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ame2.70140","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T06:43:25Z","timestamp":1773384205000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ame2.70140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/ame2.70140"],"URL":"https:\/\/doi.org\/10.1002\/ame2.70140","archive":["Portico"],"relation":{},"ISSN":["2576-2095","2576-2095"],"issn-type":[{"value":"2576-2095","type":"print"},{"value":"2576-2095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-09-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}