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

Clinical Immunology : the Official Journal of the Clinical Immunology Society
Yun Shin ChungSung Joo Kim

Abstract

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 hybrid...Continue Reading

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Citations

Feb 16, 2018·Immunology·Jessica Katy SkeltonMarcus Dorner
Oct 3, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·H-S LeeJ Yang
Apr 11, 2020·Molecular Carcinogenesis·J Jason MortonAntonio Jimeno
Jul 20, 2019·Balsaeng'gwa saengsig·Ji Yoon LeeDong Ryul Lee
Mar 11, 2017·Human Vaccines & Immunotherapeutics·J TorresiM Pellegrini
Dec 22, 2019·Virologica Sinica·Tian-Jiao FanJian-Hua Wang
Jul 27, 2021·Current Opinion in Oncology·Nuria KoteckiAhmad Awada

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