The use of severe combined immunodeficiency mice to study the metabolism of human immunoglobulin g

Background. Although the four human immunoglobulin G (IgG) isotypes are similar in structure, they exhibit significant differences in effector function and catabolic half‐life. With advent of structurally engineered antibodies, there is the potential to design antibody constructs with desired half‐lives however, it is first necessary to discover the structures and mechanisms that control immunoglobulin metabolism. Methods. Radioiodinated chimeric antibodies, consisting of a mouse antidansyl variable region and the four human IgG constant regions, were injected intravenously into Balb/c and severe combined immunodeficiency (SCID) mice, and their half‐lives were determined by whole body and whole blood counting. Dependence of the rate of immunoglobulin catabolism on immunoglobulin concentration, a normal regulatory phenomenon specific to IgG, was evaluated by the introduction of large amounts of human gamma‐globulin intraperitoneally. Results. Whole body and blood half‐lives were statistically indistinguishable. The four IgG isotypes were eliminated from the whole animals in a predominantly single‐phasic manner, with the half‐life being dependent on the isotype studied. In Balb/c mice, immune elimination frequently occurred after 6 days, although this was not observed in SCID mice. Relevance of the model was confirmed by the demonstration of the presence of the concentration‐catabolism phenomenon, a relationship unique to normal IgG regulation. Conclusions. SCID mice provide an adequate initial animal model for antibodies. Further understanding of the factors governing immunoglobulin catabolism can be probed by study of recombinant human constant regions in this animal system. Cancer 1994; 73:794–9.