Co-transplantation of human fetal thymus, bone and CD34+ cells into young adult immunodeficient NOD/SCID IL2Rγnull mice optimizes humanized mice that mount adaptive antibody responses

Yun Shin Chung, Jin Kyung Son, Bongkum Choi, Sung Yeon Joo, Yong Soo Lee, Jae Berm Park, Hana Moon, Tae Jin Kim, Se Ho Kim, Seokmann Hong, Jun Chang, Myung Soo Kang, Sung Joo Kim

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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 IL2Rγnull (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.

Original languageEnglish
Pages (from-to)156-165
Number of pages10
JournalClinical Immunology
Volume157
Issue number2
DOIs
StatePublished - 1 Apr 2015

Keywords

  • Bone
  • CD34 cells
  • Hematopoiesis
  • Humanized mice
  • Thymus
  • Young adult NOD/SCID IL2Rγ

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