FUNCTIONAL-HETEROGENEITY OF IN-VITRO SELECTED VARIANTS FROM AN IGM-SECRETING RAT IMMUNOCYTOMA

A long-term tissue culture line of highly metastatic IR202 immunocytom a of LOU rats, and five of its clones (B4, C2, C4, C5, and D3) were es tablished and studied comparatively. All such cells were similar in te rms of: (i) light microscopic morphology, (ii) growth rate, (iii) satu ration density, (iv) cell cycle progression, and (v) cell surface IgM, major histocompatibility complex (MHC) class I and class II antigen e xpression, but (vi) showed a non-homogeneous pattern of chromosomal co nstitution, with both numerical and structural abnormalities detected in variable proportions of the different cell variants. Moreover, IR20 2 variants exhibited a marked difference in the production of soluble factors which was closely associated with the ability of their superna tants to inhibit mitogen (affinity-purified goat F(ab')(2) fragments s pecific for rat mu-chains (anti-mu antibody), lipopoly saccharide (LPS ), or concanavalin A (ConA))-induced proliferation of normal splenic B and/or T lymphocytes. These results are consistent with the concept o f intratumor heterogeneity and the ability of immunoglobulin-secreting tumors to induce severe immune dysfunction in host animals and humans .