Expression of mouse mammary tumor virus superantigen accelerates tumorigenicity of myeloma cells

To investigate whether superantigen (SAG) from endogenous mouse mammary tum or virus functions as an immunogenic or a tumorigenic fatter in tumor devel opment, the BALB/c myeloma cell line FO was transfected with the SAG gene f rom the 3' Mtv-50 long terminal repeat (LTR) open reading frame (ORF), the product of which was specific for V beta 6. All five transfectants expressi ng Mtv-50 LTR ORF mRNA showed stimulatory activity for V beta 6 T-cell hybr idomas in vitro; this activity was inhibited by the addition of anti-Mtv-7 monoclonal antibody (MAb) or anti-major histocompatibility complex class II I-A(d) and I-Ed MAb. All transfectants with the SAG gene grew more rapidly than did mock transfectants in BALB/c mice after subcutaneous inoculation, whereas all clones, including mock transfectants, grew equally well in athy mic nude mice. A significant fraction of V beta 6 T cells selectively expre ssed activation markers, including CD44(high), CD62(low), and CD69(high), a nd produced large amounts of interleukin 5 (IL-5) and IL-6 in BALB/c mice i noculated with transfectants. These results suggested that the expression o f viral SAG enhances the tumorigenicity of a myeloma cell line through the stimulation of SAG-reactive T cells.