Circulating immune complexes, antigens, and antibodies related to the murine mammary tumor virus in C3H mice

A comparative study was performed to measure levels of free antibody to MuMTV, MuMTV membrane antigen (gp52), and antigen-antibody complexes in sera of mammary tumor-bearing and age-matched (10-17 mo) nontumor bearing C3H/Bi mice. Approximately 90% of these mice spontaneously develop breast cancer. Levels of MuMTV antibody and C3-containg circulating immune complexes (CIC) were highest in the sera of the mice without overt evidence of breast cancer. MuMTV gp52 antigen, however, was present in higher concentrations in the sera of mice with overt breast cancer. Fractionation of the sera on sucrose gradients followed by analysis for CIC by the complement- (C)dependent Raji radioimmunoassay and anti-C3 F(ab')₂ enzyme-linked immunosorbent assay (ELISA) confirmed that levels of C-containing CIC were lower in sera from mice with tumors than in nontumor bearers. The CIC were, however, of smaller size in sera of tumor-bearing mice. When the sera were assayed for CIC by the C-independent bull sperm ELISA, in which C binding does not compete with binding of CIC to the sperm, the levels of these small-sized CIC in sera of mice with breast cancer were now comparable to CIC levels in nontumor-bearing mice. MuMTV antibody, detected by an ELISA, was located in both 7S and high m.w. regions of the gradients. To determine whether the CIC contained MuMTV antigen, the CIC were bound to bull sperm Fc receptors and assayed for reactivity with monospecific goat anti-gp52IgG. Significantly higher levels of reactivity to anti-gp52 were detected in CIC from C3H mice than in CIC from sera of age-matched AKR mice with or without leukemia (p < 0.001) or from MRL/MpJ-Ipr/Ipr mice (p < 0.001). These data indicate that there is a shift from MuMTV antibody excess to MuMTV antigen excess and from larger C-fixing CIC to smaller non-C-fixing CIC after appearance of overt breast cancer in C3H mice.