A possible mechanism of inability of immunoglobulin heavy-chain production in Bence-Jones type myeloma cells.

To clarify the mechanism of the inability of immunoglobulin heavy (IgH) chain production in Bence-Jones (BJ) type myeloma cells, we examined the rearrangement of the IgH gene, the expression of IgH mRNA and the presence of functional nuclear factors that bind to the IgH gene enhancer in myeloma cells from 6 cases of BJ-type myelomas, and three myeloma cell lines and one Epstein-Barr virus-transformed B cell line having no IgH chain production. All BJ-type myeloma cells we examined showed rearranged bands by Southern blotting using the JH probe, and the rearrangement of VDJ segments in these cells was confirmed by PCR amplification of VDJ segments with consensus VH and JH primers. However, the expressions of IgH mRNA were not detected by Northern blotting in any of the BJ-type myeloma cells or the three non-producer myeloma cell lines. These findings suggested that the transcription of the IgH gene ceased in these cells, and alteration of this transcriptional apparatus may explain this inability. The functional nuclear factors that bind to IgH gene enhancers (HE2 and HE3) were absent in the myeloma cells from one case of BJ-type myelomas among these BJ-type myeloma cells and myeloma cell lines. This suggests that alteration of the enhancer binding factors may be one of the reasons why BJ-type myeloma cells are unable to produce the IgH chain.