Improved B cell development in humanized NOD-scid IL2Rγnull mice transgenically expressing human stem cell factor, granulocyte-macrophage colony-stimulating factor and interleukin-3.

Abstract

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 IL2Rγnull (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.

• Authors: Sonal Jangalwe, Leonard D Shultz, Anuja Mathew, Michael A Brehm
• Journal: Immunity, inflammation and disease (Immun Inflamm Dis) Vol. 4 Issue 4 Pg. 427-440 (12 2016) ISSN: 2050-4527 [Print] England
• PMID: 27980777 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Interleukin-3
• Stem Cell Factor
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Animals
• B-Lymphocytes (cytology, immunology)
• Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)
• Humans
• Interleukin-3 (metabolism)
• Mice
• Mice, Inbred NOD
• Mice, Transgenic
• Stem Cell Factor (metabolism)