Human immunoglobulin production in immunodeficient mice: enhancement by immunosuppression of host and in vitro activation of human mononuclear cells

Abstract

SUMMARY The affect of host and donor related factors on successful cngraftmenl of human cells into mice was examined to minimize the variability lhal has been observed in successful development of human mouse chimera for the study of human disease and immune physiology and regulation. Human immunoglobulin production in severe combined immunodeficiency (SCID) mice engrafted with human peripheral blood mononuclear cells (PBMC) was augmented by immunosupprcssing recipient mice and activating donor PBMC. Immunosuppression of recipient mice with 3 Gy of γ- irradiation induced a 10-fold increase in human igG in the sera of engrafted SCID mice. Variation in production of human IgG in recipient mice correlated with preinjection phenotype and activation status of injected PBMC. Mice injected with PBMC with a low CD4/CD8 ratio (less than 0·5) produced no delectable circulating human immunoglobulin. When the CD4./CD8 ratio was greater than 1·5. human IgG was detected in sera of PBMC-recipient SCID mice. Serum IgG increased 10-fold following in vitro activation of donor PBMC with anti-CD3. IL-2 and Slaphylococcus aureus. Successful engraflment and serum IgG production was evidenced by an increase in the recovery of activated human IgG cells in the spleens of mice with maximal IgG production. Optimization of functional engraftment required modification of both the host (SCID mice) and the donor cells.