Myeloma kappa gene transcription is blocked upon fusion with fibroblasts.

Numerous studies on somatic cell hybrids have shown that expression of tissue-specific functions can be suppressed as a consequence of fusion with cells that do not express the given functions. We have further investigated this phenomenon, using as a model system the regulation of expression of kappa light chain genes in intraspecific hybrids between mouse myeloma cells and mouse fibroblasts. Hybrids containing only one genome equivalent from each parent cell (1s:1s) were isolated by fluorescence-activated cell sorting from within 10 h after fusion, and they were grown for no more than 16 days thereafter in order to ensure maximum integrity of the genomic constitution. Here we report that in hybrid cells, kappa gene transcription was specifically turned off as demonstrated by nuclear run-on assays performed on 16-day-old proliferating hybrids. Furthermore, a mechanism affecting mRNA stability may also contribute, at least initially, to the rapid depletion of cytoplasmic kappa transcripts, observed during the first few hours after fusion. Suppression was dominant and could not be overridden by increasing the relative myeloma ploidy at either the heterokaryon or the synkaryon stage. Nor could suppression be relieved by treating hybrids with cycloheximide.