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Updated: Mar 10, 2026
Humanized NOD/SCID/IL2rγnull (hu-NSG) Mouse Model for HIV Replication and Latency Studies
Published on: January 7, 2019
Improved B cell development in humanized NOD-scid IL2Rγ mice transgenically expressing human stem cell factor,
Sonal Jangalwe1, Leonard D Shultz2, Anuja Mathew3
1Program in Molecular Medicine, Diabetes Center of Excellence™ University of Massachusetts Medical School Worcester Massachusetts 01605 USA.
Introduction:
Immunodeficient mice engrafted with human immune systems support studies of human hematopoiesis and the immune response to human-specific pathogens. A significant limitation of these humanized mouse models is, however, a severely restricted ability of human B cells to undergo class switching and produce antigen-specific IgG after infection or immunization.
Methods:
In this study, we have characterized the development and function of human B cells in NOD-scid IL2Rγ (NSG) mice transgenically expressing human stem cell factor (SCF), granulocyte macrophage colony-stimulating factor (GM-CSF), and IL-3 (NSG-SGM3) following engraftment with human hematopoietic stem cells, autologous fetal liver, and thymic tissues (bone marrow, liver, thymus or BLT model). The NSG-SGM3 BLT mice engraft rapidly with human immune cells and develop T cells, B cells, and myeloid cells.
Results:
A higher proportion of human B cells developing in NSG-SGM3 BLT mice had a mature/naive phenotype with a corresponding decrease in immature/transitional human B cells as compared to NSG BLT mice. In addition, NSG-SGM3 BLT mice have higher basal levels of human IgM and IgG as compared with NSG BLT mice. Moreover, dengue virus infection of NSG-SGM3 BLT mice generated higher levels of antigen-specific IgM and IgG, a result not observed in NSG BLT mice.
Conclusions:
Our studies suggest that NSG-SGM3 BLT mice show improved human B cell development and permit the generation of antigen-specific antibody responses to viral infection.
