Naturally occurring humoral immunity to endogenous xenotropic and amphotropic type-C virus in the mouse

Natural humoral cytotoxic antibodies from 13- and 18-month-old BALB/c mice showed a virus-specific complement-dependent activity against target cells productively infected with xenotropic, amphotropic or ecotropic type-C viruses. The cytotoxic activity was lowest against ecotropic virus-shedding cells. Serum obtained from mice less than 12 months old had no such reactivity. The cytotoxic reactivity was found to reside solely in the immunoglobulin M fraction which yielded reactivity comparable to the unfractionated sera concerning both titer and relative reactivities to the target cells infected with different type-C viruses. In hyperimmune mouse serum cytotoxic reactivity resided in IgG and IgM fractions. Examination of serum from individual, normal 18-month-old BALB/c mice revealed that 80-90% of them were cytotoxic against virus non-producer mink target cells expressing gp70 or gaggene product. Absorption of sera from 18-month-old normal BALB/c mice with cells shedding Class II or Class III xenotropic virus, amphotropic virus, Rauscher-MuLV, or Class 1 murine leukemia virus indicate a closer amphotropic-FMR viral subtype specificity of the natural cytotoxic immune response as compared to the amphotropic-xenotropic or amphotropic-ecotropic specificity. The incidence and the level of measured humoral cytotoxic activity was sustained in the tumor-bearing animal up to 28 months of age as compared to the background established in the 18-month-old animal. However, in the non-tumor-bearing animal, the incidence and level of cytotoxic reactivity declined rather rapidly with aging. Te sustained cytotoxic reactivity of the serum from old tumored mice might be involved in the progression of the tumor.