Human B cell development and antibody production in humanized NOD/SCID/IL-2Rγ(null) (NSG) mice conditioned by busulfan

J Clin Immunol. 2011 Apr;31(2):253-64. doi: 10.1007/s10875-010-9478-2. Epub 2010 Oct 28.

Abstract

Background: Busulfan treatment as a chemotherapeutic agent has been considered an alternative approach in xenograft model because it offers a simple, convenient, effective, and less toxic conditioning regimen.

Objective and methods: To investigate busulfan effects on the reconstitution of human immune cells and the generation of immune response to foreign antigens, we generated humanized NOD/SCID/IL-2Rγ(null) (NSG) mice conditioned either busulfan or total body irradiation (TBI) with hCD34(+) CB cells.

Results: Busulfan resulted in a high survival rate and effective reconstitution of human immune cells including B, T, macrophage, and dendritic cells in humanized NSG mice, compared to that of TBI. Moreover, the humanized NSG mice conditioned busulfan showed effective B cell development and thereby the high production of human antibody against immunized antigen.

Conclusion: Humanized mice conditioned by busulfan provide a powerful and versatile tool for studying the entire process of human B-lymphocyte development and for producing specific human antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antibody Formation / drug effects*
  • Antibody Formation / immunology*
  • Antibody Formation / radiation effects
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / radiation effects
  • Busulfan / pharmacology*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunocompromised Host / drug effects*
  • Immunocompromised Host / radiation effects
  • Interleukin Receptor Common gamma Subunit / genetics
  • Lethal Dose 50
  • Lymph Nodes / cytology
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • Survival Analysis
  • T-Lymphocytes / immunology
  • Whole-Body Irradiation

Substances

  • Adjuvants, Immunologic
  • Interleukin Receptor Common gamma Subunit
  • Busulfan