Autogenous immunity to endogenous RNA tumor virus: Differential reactivities of immunoglobulins M and G to virus envelope antigens

The autogenous humoral immune response of mice to their endogenous leukemia virus has been examined in terms of the reactivities of individual classes of antibody present in normal B6C3F₁ serum. Whole serum and the immunoglobulin (Ig) M and IgG fractions of serum from animals of different age groups were compared by radioimmune precipitation assays and viral infectivity neutralization assays. Both IgM and IgG fractions were able to precipitate virus, although not as effectively as whole serum. Virus specific antibody levels, as well as total antibody concentrations in whole serum, appeared to increase with age. Sodium dodecyl sulfate gel electrophoresis analysis was performed with immune precipitates obtained when whole serum or 19 or 7S fractions from animals of different age groups were reacted with disrupted virus. The 19S antibody fraction reacted with three antigenic determinants on the viral envelope. These antigens have apparent molecular weights of 17,000, 43,000, and 68,000. The last two appear to be glycoproteins and may correspond to the M₂ and M₁ antigens. In contrast, the 7S component reacted only with the 17,000 molecular weight protein. Neutralization assays against BALB:virus 2, a xenotropic endogenous mouse type C virus, revealed that 19S and whole serum but not the 7S fraction possessed neutralizing activity. These findings indicate that there are differential reactivities of IgM and IgG antibodies in normal serum of B6C3F₁ mice, with respect to both recognition of viral envelope antigens and neutralization of endogenous MuLV. These results are consistent with the hypothesis that the autogenous humoral immune response is a systemic host function that may be important in the regulation of endogenous type C virus expression in vivo.