Restoration of a tumorigenic phenotype by β2-microglobulin transfection to EL-4 mutant cells

Abstract

It has frequently been suggested that loss of β2-microglobulin (β2m) in tumor cells may lead to malignant progression due to escape from immunological recognition. Here, we directly tested the role of β2m expression in tumorigenicity. A β2m 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 C57B1/6 (B6) mice. The reduced tumorigenicity was directly related to β2m expression. Transfection of an intact murine β2m gene markedly increased the tumorigenic potential. The reduced tumorigenicity of C4.4-25- compared with β2m 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 β2m 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.