The hu-PBL-SCID mouse model. Long-term human serologic evolution associated with the xenogeneic transfer of human peripheral blood leukocytes into SCID mice.
We present a 2-year serologic analysis of severe combined immune deficiency (SCID) mice populated with human peripheral blood leukocytes (PBL, hu-PBL-SCID mice). After 10-20 x 10(6) PBL transfer, human IgG serum levels generally increased in the SCID mouse recipient for 2 months, and thereafter decreased without returning to zero for at least 2 years. Great variability existed between different hu-PBL-SCID mice with regard to Ig serum levels even when derived from the same donor's PBL aliquot. The ratio of IgM to IgG serum levels was lower in hu-PBL-SCID mice than in the donors. The half-life of human IgG in the SCID mouse is shorter than in the human (8 days vs 23 days), suggesting a much higher production of IgG than expected from serum levels. The majority of hu-PBL-SCID mouse sera analyzed by high resolution electrophoresis had a smear appearance suggestive of diverse human Ig, generally with superimposed multiple faint mIg. Few mice developed strong human mIg, associated with lymphoproliferative diseases. In the hu-PBL-SCID mouse model, the transfer of cells from donors making antibody with defined specificity against TT and nuclear antigen resulted in the appearance of these antibodies in only a minority of the recipients.
Duchosal
M A
MA
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Eming
S A
SA
McConahey
P J
PJ
Dixon
F J
FJ
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D000907:Antibodies, Bacterial / Q000032:analysis; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D017708:Leukocyte Transfusion; D007962:Leukocytes / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID / Q000276:immunology*; D008954:Models, Biological; D013745:Tetanus Toxoid / Q000276:immunology; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology
D000974:Antibodies, Antinuclear; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D013745:Tetanus Toxoid