DOI: 10.1002/ame2.70140
A humanized NOG-EXL mouse model for producing severe fever with thrombocytopenia syndrome virus-reactive human antibodies
Dong Hoon Lee1
Jiyeong Bae2
Sumi Kim1
Chan Young Song3
Jung Hyu Shin3
Eun Hee Kim3
Chan Ho Jang3
Young-sun Yun1
Dong-sook Lee1
Hyuk Chu1
Jang-Hoon Choi1
Chan Woo Kim3
1.Division of Acute Viral Diseases,Center for Emerging Virus Research,National Institute of Infectious Diseases,National Institute of Health,Cheongju,Korea2.Experimental Evaluation Department,Non-Clinical Evaluation Center,OSONG Medical Innovation Foundation(KBIOHealth),Cheongju,Korea;College of Pharmacy and Medical Research Center,Chungbuk National University,Cheongju,Korea3.Experimental Evaluation Department,Non-Clinical Evaluation Center,OSONG Medical Innovation Foundation(KBIOHealth),Cheongju,Korea
摘要：Background:Humanized mouse models are essential for studying the human im-mune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To overcome these limitations,we used the NOG-EXL mice expressing human interleukin 3(IL-3)and granulocyte-macrophage colony-stimulating factor(GM-CSF)to enhance myeloid and B-cell lineage differentiation.
Methods:Human CD34+hematopoietic stem cells(HSC)were transplanted into NOG-EXL mice to produce humanized immune systems.After immune cell reconstitu-tion was confirmed across 12 weeks,the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus(SFTSV)antigens.Peripheral blood mononuclear cells and splenocytes were analyzed using multicolor flow cytom-etry to assess human immune cell subsets.Antigen-specific immunoglobulin G(IgG)production was quantified using enzyme-linked immunosorbent assay(ELISA),and virus-specific B cells were isolated using antigen-labeled recombinant protein probes.
Results:Twelve weeks after transplantation of HSCs into NOG-EXL mice,they ex-hibited robust engraftment of human leukocytes,including T,B,and dendritic cells,compared to NOG mice.Unlike NOG mice,humanized NOG-EXL mice exhibited an increase in human IgG levels,indicating the production of human antibody responses to antigens.Humanized NOG-EXL mice were immunized twice every 2weeks with inactivated SFTSV,and antigen-specific human antibodies against the virus were de-tected in the mouse sera by ELISA.Sera from SFTSV-immunized humanized mice dem-onstrated neutralizing activity against SFTSV,confirming the induction of functional virus-specific neutralizing antibodies.Antigen-binding IgG-positive human B cells were isolated from mouse splenocytes using recombinant protein probes.
Conclusion:This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high-affinity human monoclonal antibodies without genetic engineering.
机标关键词：mousemodelwithantibodiesfeverhrombocytopeniahumanizedproducing
论文发表日期：2026-02-28
在线出版日期：2026-03-31（本平台首次上网日期，不代表文献的发表时间）
页数：11( 378-388 )
英文信息