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

Clin Immunol. 2015 Apr;157(2):156-65. doi: 10.1016/j.clim.2015.02.005. Epub 2015 Feb 25.


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.

Keywords: Bone; CD34(+) cells; Hematopoiesis; Humanized mice; Thymus; Young adult NOD/SCID IL2Rγ(null).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology*
  • Animals
  • Antibodies / immunology*
  • Antibody Formation
  • Antigens, CD34 / metabolism*
  • Bone Transplantation*
  • Fetal Tissue Transplantation*
  • Hematopoiesis
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / metabolism*
  • Heterografts
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Interleukin Receptor Common gamma Subunit / genetics
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Spleen / immunology*
  • Spleen / pathology
  • Thymus Gland / transplantation*


  • Antibodies
  • Antigens, CD34
  • Il2rg protein, mouse
  • Immunoglobulin G
  • Immunoglobulin M
  • Interleukin Receptor Common gamma Subunit