H‐2 control of the cytotoxic antibody response against a newly defined MuLV‐related cell‐surface antigen: G_(B10.A)

Abstract

H-2-congeneic C57BL mice with milk transmission of B-tropic murine leukemia virus (V+ mice) have a much higher lymphoma incidence than the same strains without milk-transmitted virus (V- mice). Gene(s) within the major histocompatibility complex (H-2) influence virus titers, lymphoma incidence, lymphoma type and the anti-MuLV envelope antibody response. In this paper, we report that the prevalence of cytotoxic antibodies to virus-induced lymphomas is also regulated by the H-2 complex. Milk transmission of MuLV resulted in the formation of cytotoxic antibodies against primary virus-induced C57BL lymphomas. These antibodies detect an antigen that is also present on the RADAI tumor-cell line, and on normal spleen cells of young adult B10.A (H-2a) mice of both V+ and V- sublines, but not on spleen cells of young adult B10 (H-2a) mice of either subline. These cytotoxic antibodies were detected in the sera of B10V+ and B10.A(5R)V+ animals, but not in the sera of B10.AV+ mice. This indicates that the prevalence of these antibodies is controlled by a gene in the K- and/or I-A region of the H-2 complex. The presence of these cytotoxic antibodies in serum is recessively inherited. The specificity of the cytotoxic antibodies was investigated with a standard panel of transplantable tumor-cell lines. Of these, only the RADAI cells expressed the target antigen in direct cytotoxicity tests and by absorption. The ability of B10V+ sera to lyse the B10.AV+ and RADAI tumor cells is ascribed to antibody activity against a new MuLV-related cell-surface protein: G(B10.A). Immunochemical analysis and absorption experiments with different types of purified MuLV and MuLV-infected cell lines indicate that the cytotoxic antibodies belong to low-avidity IgM antibodies that are directed to MuLV.

Cooperation between cytotoxic and helper T lymphocytes in protection against lethal Sendai virus infection. Protection by T cells is MHC-restricted and MHC-regulated; a model for MHC-disease associations.

“…A direct link between MHC type and susceptibility to acute viral illness has not been established before . On the other hand, the association between MHC type and susceptibility to chronic disease induction by RNA tumor viruses, where immune mechanisms are probably responsible for protection, is well established (36)(37)(38)(39)(40)(41)(42). In this case, again, the ability to generate a strong MHC-regulated immune response is associated with resistance to the induction of disease.…”

Major histocompatibility complex class II-regulated immunity to murine leukemia virus protects against early T- but not late B-cell lymphomas

“…MuLV-induced lymphomagenesis has been a model of MHC-disease association since first reported by Lilly and colleagues many years ago (28). Several immune mechanisms have been postulated to explain the MHC influence on lymphoma susceptibility, including regulation of antibody response against virus-induced tumor cells (12,47,55), proliferative T-cell responses (4), and regulation of cytotoxic T-cell (TJ) reactivity (20). Tc effectiveness may also be influenced by another postulated mechanism, namely, MHC allelic differences in class I MHC expression on virusinfected cells (32).…”

Retrovirally induced murine B‐cell tumors rarely show proviral integration in sites common in T‐cell tumors

“…We have previously shown that the interaction of the immune system with virus and virally infected cells (Vlug et al, 1981(Vlug et al, , 1983Vasmel et al, 1988) strongly influences the latency and phenotype of lymphomas in this system. We now show that this influence extends to the mechanisms of tumorigenesis of B-and T-cell lymphomas, albeit indirectly.…”