Human B Cell Development and Antibody Production in Humanized NOD/SCID/IL-2Rγnull (NSG) Mice Conditioned by Busulfan

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. 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-2R gamma(null) (NSG) mice conditioned either busulfan or total body irradiation (TBI) with hCD34(+) CB cells. 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. 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.