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Differential Antigenic Expression of the DBA/2 Lymphoma L1210 and Its Sublines: Cross-Reactivity with C3H Mammary Tumors as Defined by Syngeneic Monoclonal Antibodies¹

Department of Molecular Immunology, Roswell Park Memorial Institute,^,3 Buffalo, New York 14263

The expression of tumor-associated antigens on the DBA/2 lymphoma L1210 and three L1210 sublines, each resistant to a different antileukemic agent [guanazole, methylglyoxal-bis(guanylhydrazone), and 4,4-diacetyldiphenylurea-bis(guanylhydrazone)] was investigated by the use of monoclonal hybridoma antibodies. Hybridomas were produced by the fusion of spleen cells from DBA/2 mice immunized with irradiated L1210 or L1210 subline cells and cells of a non-immunoglobulin-secreting BALB/c myeloma variant. Three clones producing antibodies reacting with L1210 or L1210 subline cells were used to study the antigenic expression of L1210 and L1210 subline cells.

Monoclonal antibodies from anti-L1210 and anti-L1210 subline hybridomas exhibited a greater reactivity with L1210 subline cells than with L1210 cells in complement-dependent cytotoxicity, quantitative absorption, and membrane immunofluorescence experiments, thereby demonstrating a tumor-associated antigen shared by L1210 and the L1210 sublines and an increased expression of this antigen on subline cells. Cross-blocking tests of antibody binding demonstrated that monoclonal antibodies from anti-L1210 and anti-L1210 subline hybridomas recognized the same or very closely situated antigenic determinants on the tumor cell surface. Most syngeneic and allogeneic tumor cells used as controls failed to react with the anti-L1210 and anti-L1210 subline hybridoma antibodies. However, two syngeneic tumors, L5178Y and P388-D1, demonstrated a significant reaction with the monoclonal antibodies. In addition, several spontaneous mammary tumors from C3H/St and DBA/2Ha, both high-frequency mammary tumor strains, reacted in various degrees with anti-L1210 or anti-L1210 subline hybridoma antibodies in absorption tests and in immunofluorescence experiments. On the other hand, liver, kidney, and spleen from normal C3H/St mice, as well as mammary tumors from BALB/c and C3Hf, both low-frequency mammary tumor strains, did not demonstrate significant reactivity in similar experiments. Normal lactating mammary glands from high-frequency mammary tumor mouse strains reacted with the monoclonal antibodies, whereas lactating mammary glands from low-frequency mammary tumor mouse strains were negative by this method. Purified murine mammary tumor virus preparations reacted strongly with the monoclonal antibodies in solid-phase radioimmunoassays, whereas a purified murine leukemia virus preparation failed to do so in similar experiments. These results indicate that the tumor-associated antigen(s), differentially expressed on L1210 and L1210 subline cells, is related to an antigen which is associated with the murine mammary tumor virus.

¹ This work was supported in part by Grants CA-26479, CA-26942, and CA16056, awarded by the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed.

³ A unit of the New York State Department of Health.

Received 6/24/82. Accepted 2/23/83.