title: Improved B cell development in humanized NOD-scid IL2Rγnullmice transgenically expressing human stem cell factor, granulocyte-macrophage colony-stimulating factor and interleukin-3.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Program in Molecular Medicine, Diabetes Center of Excellence™ University of Massachusetts Medical School Worcester Massachusetts 01605 USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Jangalwe
authors.affiliation: The Jackson Laboratory Bar Harbor Maine 04609 USA.
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Shultz
authors.affiliation: Department of Cell and Molecular Biology University of Rhode Island Providence Rhode Island 02903 USA.
authors.forename: Anuja
authors.initials: A
authors.lastname: Mathew
authors.affiliation: Program in Molecular Medicine, Diabetes Center of Excellence™ University of Massachusetts Medical School Worcester Massachusetts 01605 USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Brehm
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D019089:Stem Cell Factor / Q000378:metabolism*
chemical_list: D007377:Interleukin-3; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: B cells; SCID; cytokine; hematopoietic stem cells; humanized mice