Endogenous Mtv-8 or a closely linked sequence stimulates rearrangement of the downstream V kappa 9 gene

Abstract

Mtv-8 is an endogenous retrovirus located 4.6 kb upstream of a V kappa region gene (called V kappa 9M) within the kappa-Ig locus. The proximity of these two genes resulted in several effects. Using a newly developed RNase protection assay for measuring transcription from a single endogenous provirus, we found that Mtv-8 transcription could be detected after juxtaposition of the kappa-enhancers to the normally silent provirus. Reciprocally, using the polymerase chain reaction we observed that the frequency of V kappa 9M rearrangement was 5- to 10-fold higher in spleens from Mtv-8-positive mice (BALB/c, C58.C, A/J, and B6) compared to spleens from mice that lacked the Mtv-8 provirus (C58, C.C58, NZB, and PERA/Ei). Molecular cloning and sequencing of the V kappa 9M gene from C.C58 mice (containing the kappa-locus from C58 mice on a BALB/c background) indicated that at least some Mtv-8-negative strains have a functional V kappa 9M gene. Together these data suggest that Mtv-8 or a closely linked gene enhances V kappa 9M rearrangement. Since Mtv-8 also reportedly produces a superantigen, it appears that Mtv-8 may influence both the T cell and B cell repertoires.