Clonal variation in tumorigenicity of L1210 lymphoma cells: nontumorigenic variants with an enhanced expression of tumor-associated antigen and Ia antigens.

Clonal variations in the tumorigenicity and in the expressions of tumor-associated antigens (TAA) as well as normal cell surface antigens were studied using clones of a highly tumorigenic DBA/2 lymphoma, L1210, which were isolated by limiting dilution in vitro. The majority of the clones were highly tumorigenic (tum+) in normal syngeneic mice, as was the parent L1210. The rest were nontumorigenic (tum-) in such mice; these clones, however, were tumorigenic in host mice that had been immunosuppressed by irradiation with 450 rads. Moreover, these tum- variants were shown to have an ability to elicit, in syngeneic mice, strong host resistance specifically directed against challenge with the parent L1210 and tum+ cloned cells and an ability to generate an in vitro primary syngeneic cytotoxic T-cell response against L1210 clones, indicating an enhanced immunogenicity in tum- variants. The expression of TAA by tumor clones was defined by determining the reactivity of monoclonal antibody, raised in syngeneic mice against an immunogenic L1210 subline, L1210/GZL. Marked clonal variation in the expression of monoclonal antibody-defined TAA was demonstrated, while no significant variation was seen in the H-2Dd expression. There was an inverse relationship between the TAA expression and the tumorigenicity. Furthermore, the enhanced expression of the TAA and the increased immunogenicity was associated with the I-Ad expression on the tum- variants. The unique characteristics of the tumor variants were very stable and heritable although occasional revertant phenotypes were detected on some clones. The results suggest that the tumor variants bearing distinct immunological properties exist in the parent L1210 line and carry a potential to modulate host immune responses directed against tumor cells.