GM-CSF and IL-4 stimulate antibody responses in humanized mice by promoting T, B, and dendritic cell maturation

J Immunol. 2012 Dec 1;189(11):5223-9. doi: 10.4049/jimmunol.1201789. Epub 2012 Oct 22.


Engraftment of human hematopoietic stem cells into immunodeficient mice that lack T cells, B cells, and NK cells results in reconstitution of human blood lineage cells, especially B cells, in the recipient mice. However, these humanized mice do not make any significant level of IgG Ab in response to Ag stimulation. In this study, we show that in humanized mice, B cells are immature, and there is a complete deficiency of CD209(+) (DC-SIGN) human dendritic cells. These defects can be corrected by expression of human GM-CSF and IL-4 in humanized mice. As a result, these cytokine-treated humanized mice produced significant levels of Ag-specific IgG after immunization, including the production of neutralizing Abs specific for H5N1 avian influenza virus. A significant level of Ag-specific CD4 T cell response was also induced. Thus, we have identified defects in humanized mice and devised approaches to correct these defects such that the platform can be used for studying Ab responses and to generate novel human Abs against virulent pathogens and other clinically relevant targets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / immunology*
  • Antigens, Viral / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Differentiation
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Fetus
  • Founder Effect
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Humans
  • Immunocompromised Host*
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / immunology
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology*
  • Liver / cytology
  • Liver / immunology
  • Mice
  • Mice, Transgenic / immunology
  • Orthomyxoviridae Infections / genetics
  • Orthomyxoviridae Infections / immunology
  • Plasmids
  • Single-Cell Analysis
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Transfection


  • Antibodies, Viral
  • Antigens, Viral
  • IL4 protein, human
  • Immunoglobulin G
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor