RESTORATION OF A TUMORIGENIC PHENOTYPE BY BETA-2-MICROGLOBULIN TRANSFECTION TO EL-4 MUTANT-CELLS

It has frequently been suggested that loss of beta-2-microglobulin (beta-2m) in tumor cells may lead to malignant progression due to escape from immunological recognition. Here, we directly tested the role Of beta-2m expression in tumorigenicity. A beta-2m loss mutant (C4.4-25-), selected from the murine lymphoma EL-4, showed a marked reduction in tumorigenicity as compared with EL-4 in normal C57Bl/6 (B6) mice. The reduced tumorigenicity was directly related to beta-2m expression. Transfection of an intact murine beta-2m gene markedly increased the tumorigenic potential. The reduced tumorigenicity of C4.4-25- compared with beta-2m transfected cells was observed also in athymic B6 nu/nu mice, but was abolished in B6 mice depleted of natural killer (NK) 1.1-positive cells. These results show that restoration of beta-2m expression can promote tumorigenicity and demonstrate for the first time that induction of major histocompatibility complex class I expression by transfection can lead to escape from NK cells in vivo.