Unique proliferation-associated marker expressed on activated and transformed human cells defined by monoclonal...

The expression, tissue distribution, and preliminary characterization of a cell surface molecule, apparently a glycolipid, recognized by a monoclonal antibody, anti-PAA, were described. This antibody (anti-PAA) was produced by the fusion of myeloma cells NS-1 with spleen cells from a BALB/c mouse, which were sensitized with activated human T-cells generated by allogeneic stimulation in mixed-lymphocyte culture (MLC). Resting human peripheral blood T-cells, B-cells, and monocytes demonstrated weak anti-PAA binding. Binding of proliferating T-cells (phytohemagglutinin- and MLC-activated T-cells) and thymocytes to anti-PAA was two to six times greater than that of resting T-cells. A fifteenfold-increased binding was observed with acute lymphocytic leukemia T-cell lines. Epstein-Barr virus-transformed B-cell lines bound anti-PAA up to sixteenfold greater than resting B-cells. Tumor cell lines of various nonlymphoid origins demonstrated marked reactivity with this antibody. Both benign and malignant cells in hyperplastic tissues, of various origins, bound anti-PAA, whereas their normal, nonproliferating counterparts did not. Normal proliferating cells in these tissues, including cells of the placental chorionic villi and trophoblasts, also bound anti-PAA. Of all lymphoid and nonlymphoid cell lines examined, only chronic lymphocytic leukemia (CLL) cells and some cell lines derived from Burkitt's lymphoma showed weak or no binding. This antibody also failed to react with a variety of nonprimate cell lines. Anti-PAA antibody did not immunoprecipitate any protein from lymphoid tumor cell lines to which it demonstrated a quantitatively high degree of binding, nor did protease treatment of these lines decrease antibody binding. Anti-PAA did, however, bind to glycolipids extracted from these cell lines. Binding of this monoclonal antibody to a minor neutral glycolipid, isolated from the erythroleukemia cell line K562, was about sixfold greater than that of any other K562 neutral glycolipid or ganglioside. Anti-PAA demonstrated weak or undetectable binding to purified, predominant, lymphoid cell membrane's neutral glycolipids and gangliosides. The monoclonal antibody anti-PAA appeared, therefore, to recognize a unique, proliferation-associated, neutral glycolipid present on normal as well as on benign and malignant proliferating cells. The antigen appeared to be universally expressed on proliferating cells from all human tissues with the exception of some Burkitt's cell lines and CLL cells. Nonhuman cell lines, except those for closely related primates, did not express PAA.