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

Cancer. 1994 Feb 1;73(3 Suppl):794-9. doi: 10.1002/1097-0142(19940201)73:3+<794::aid-cncr2820731308>3.0.co;2-a.

Abstract

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 the study of human-mouse chimeric antibodies. Further understanding of the factors governing immunoglobulin catabolism can be probed by study of recombinant human constant regions in this animal system.

MeSH terms

  • Animals
  • Half-Life
  • Humans
  • Immunoglobulin G / metabolism*
  • Immunoglobulin Isotypes / metabolism
  • Iodine Radioisotopes
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Recombinant Fusion Proteins

Substances

  • Immunoglobulin G
  • Immunoglobulin Isotypes
  • Iodine Radioisotopes
  • Recombinant Fusion Proteins