Characterization of the responding populations for the generation of proliferative response to syngeneic Meth A tumor in BALB/c mice: requirement of T and B cell collaboration.

High levels of primary proliferative response to a chemically induced sarcoma Meth A can be induced in syngeneic BALB/c spleen cells. Testing at the peak of proliferative response (2 days after sensitization in the mixed lymphocyte tumor cell culture), we found the responders to be resistant to anti-Thy 1.2 antibody lysis but susceptible to anti-Ia antibody lysis. When responders were subjected to various treatments before sensitization, it was found that removal of macrophages had no effect on the generation of proliferative response; high levels of proliferative response could be induced in enriched B cell preparations and in spleen cells from nude mice, but there was only a negligible amount of response in enriched T cell preparations. These findings indicate that the responders are primarily B lymphocytes. However, it was also found that the enriched B cell preparations usually gave only 50 to 75% of the response of whole spleen cells, whereas these B cells gave a 2- to 3-fold increase in the response to a B cell mitogen, LPS; this result indicate that collaboration from other types of lymphocytes was required for the generation of an optimal proliferative response to Meth A. Addition of 10% of T cells indeed produced a helper effect on this B cell response, and the maximal helper effect was seen for a mixture containing equal parts of T cells and B cells or for a slight T cell excess. These results indicate that the proliferative response to a syngeneic Meth A tumor is a macrophage-independent T-dependent B cell response.