LINKAGE OF SUPERANTIGEN-LIKE STIMULATION OF SYNGENEIC T-CELLS IN A MOUSE MODEL OF FOLLICULAR CENTER B-CELL LYMPHOMA TO TRANSCRIPTION OF ENDOGENOUS MAMMARY-TUMOR VIRUS

The MHC class II I-A(s) positive B cell lymphomas reticulum cell sarco ma (RCS) that arise in >90% of SJL mice by the age of 12 months have s uperantigen-like stimulating properties. In the present study, therefo re, RCS cell lines were examined for abnormal expression of endogenous mouse mammary tumor virus (MMTV) proviruses. Extraordinarily high exp ression of a 1.8 kb mRNA hybridizing with the long terminal repeat (LT R) of MMTV was found in both primary lymphomas and in vitro RCS lines, but not in an SJL B cell lymphoma, NJ101, that does not stimulate syn geneic T cells, or in LPS activated SJL B cells. A cDNA was cloned fro m cRCS-2 and sequenced. A 31mer oligonucleotide probe, prepared based on the unique C-terminal sequence of this RCS-Mtv LTR, detected the 1. 8 kb mRNA in all RCS lymphomas, while a similar probe for the C-termin al sequence of Mtv-8 LTR hybridized with the larger mRNA present in no rmal B cells and in NJ101. Preincubation with 19mer antisense S-oligon ucleotides, prepared based on the sequences of the first two potential translation initiation sites common to both Mtv-8 and the RCS-Mtv LTR , significantly reduced the ability of RCS cells to stimulate syngenei c T cells. Moreover, transfection of NJ101 cells with the cloned RCS-M MTV cDNA conferred Vbeta16 T cell stimulating properties on to these c ells. It is concluded that expression of the product of this MMTV-LTR mRNA provides RCS with the strong T cell stimulating properties that i t needs for its growth. These results thus identify a novel oncogenic property of MMTV-LTR.