COORDINATE SILENCING OF MYELOMA-SPECIFIC GENES IN MYELOMA X T-LYMPHOMA HYBRIDS

It has been well-established that Ig genes are transcriptionally silen ced when Ig-producing myeloma lines are fused to non-B cells. In the p resent study, we analyzed the expression of several other myeloma-spec ific genes in fusions of myelomas with the T lymphoma, BW5147. Seven o f the eight genes analyzed behaved coordinately with the Ig loci; they were silent in most myeloma x T hybrids but active in the rare hybrid that retained Ig gene expression. Cloned IgH genes introduced into th e two types of hybrids behaved as their endogenous counterparts. The c oordinate behavior of these several genes in the panel of ''exceptiona l'' and ''extinguished'' hybrids suggests a central and bimodal switch for alternately activating and de-activating the genetic program of t he Ig-secreting plasmacyte. The switch between an active and an inacti ve transcriptional state involves, at some level, a change in the meth ylation status of the IgH genes. Methylation and transcriptional activ ity were inversely correlated. In Ig-extinguished hybrids the myeloma- derived locus was methylated de novo, whereas in the rare Ig-expressin g hybrid, the T cell-derived locus was demethylated de novo.