Transplantability, immunological unresponsiveness, and loss of cellular antigenicity in gross virus lymphoma.

The capacity for syngeneic transplantation of rat lymphoma cells, originally induced by Gross lymphoma virus (GLV), was correlated with the expression of GLV-associated antigens by these cells. It was found that lymphoma cells that replicate GLV and display membrane and cytoplasmic GLV-associated antigens are consistently rejected when transplanted into syngeneic recipients. By contrast, lymphoma cells derived from the same parental cell line and morphologically indistinguishable, that have lost both surface and cytoplasmic antigenic expression were accepted and grew progressively at primary and metastatic sites. In further experiments, a long-lasting state of specific immunologic unresponsiveness was induced by administration of soluble GLV-associated antigens to newborn rats. These rats were later grafted with GLV-induced lymphoma cells that were positive for both membrane and cytoplasmic antigens. The rats conditioned at birth accepted the grafts which grew progressively, in contrast to normal controls which rejected them consistently. However, the grafted lymphoma cells showed progressive loss of antigenic determinants, and became serially transplantable in normal adult non conditioned rats. The membrane antigens were first to disappear from the grafted lymphoma cells, followed by the internal cytoplasmic antigens in further transplant generations. The transplantability of these cells increased accordingly. Titers of anti-GLV sera in tumor-bearing rats remained high even after surface antigens of lymphoma cells were no longer detected, but decreased to baseline levels after the internal antigens had been similarly lost.