Co-transplantation of human fetal thymus, bone and CD34(+) cells into young adult immunodeficient NOD/SCID IL2Rγ(null) mice optimizes humanized mice that mount adaptive antibody responses.
Both the thymus (T) and bone (B) are necessary hematopoietic niches in adult humans. We previously showed that co-transplantation of human fetal T and B tissues into neonatal immunodeficient NOD/SCID IL2Rγ(null) (NSG, N) mice facilitated hematopoiesis. However, transplantation into neonatal mice resulted in high frequency of early death, making it unrealistic for repetitive experiments. In this study, young adult N mice were pre-engrafted with T and B, T alone, B alone or no tissues. The animals were irradiated and injected with autologous fetal liver (FL)-derived CD34(+) cells (34). The resultant mice were TB34N, T34N, B34N and 34N, respectively, and challenged with T cell dependent antigens (Ags). The humanized TB34N mice showed best performance of these mouse models in many aspects resembling the adult human Ag-experienced spleen. The TB34N mice exhibited better hematopoietic reconstitution; balanced development of T- and B-cell, and common progenitor cells; follicular lymphoid structures with a functional germinal center (GC) enriched with follicular dendritic cells (FDCs) and plasma cells (PCs); secretion of hIgG in the sera in response to Ags at comparable levels to those of human; derivations of hIgG mAb-secreting hybridoma clones. Collectively, the humanized TB34N mice could develop an adaptive immunity that was capable of producing Ag-specific hIgG at a significant level via class switching. This unprecedented TB34N platform in humanized mice would be useful in dissecting human immunity, for generating human Abs and clinical applications.
Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea.
Yun Shin
YS
Chung
Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea.
Jin Kyung
JK
Son
Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea.
Bongkum
B
Choi
Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea; Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Samsung Biomedical Research Institute and Center for Future Sciences, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea.
Sung-Yeon
SY
Joo
Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea.
Yong-Soo
YS
Lee
Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea; Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jae Berm
JB
Park
Department of Pathology, Sungkyunkwan University School of Medicine, Suwon, Korea.
Hana
H
Moon
Department of Pathology, Sungkyunkwan University School of Medicine, Suwon, Korea.
Tae Jin
TJ
Kim
University-Industry Cooperation Foundation and Department of Systems Immunology, Kangwon National University, Chuncheon, Kangwon-do, Korea.
Se Ho
SH
Kim
Department of Bioscience and Biotechnology, College of Life Sciences, Sejong University, Seoul, Korea.
Seokmann
S
Hong
Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
Jun
J
Chang
Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Samsung Biomedical Research Institute and Center for Future Sciences, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea. Electronic address: mkang@skku.edu.
Myung-Soo
MS
Kang
Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea; Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Samsung Biomedical Research Institute and Center for Future Sciences, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea; Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: kmhyj111@gmail.com.
Sung Joo
SJ
Kim
D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D018952:Antigens, CD34 / Q000378:metabolism*; D016025:Bone Transplantation; D016332:Fetal Tissue Transplantation; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000637:transplantation*
D000906:Antibodies; D018952:Antigens, CD34; C507942:Il2rg protein, mouse; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D053631:Interleukin Receptor Common gamma Subunit
Bone; CD34(+) cells; Hematopoiesis; Humanized mice; Thymus; Young adult NOD/SCID IL2Rγ(null)