COEXPRESSION OF MU AND LAMBDA-1 HEAVY-CHAINS CAN OCCUR BY A DISCONTINUOUS TRANSCRIPTION MECHANISM FROM THE SAME UNREARRANGED CHROMOSOME

We previously documented that a single BCL1 leukemia cell can produce mu and gamma-1 immunoglobulin heavy chains with identical variable segments in an allelically excluded fashion without heavy chain constant region gene rearrangement. To understand the mechanism of dual mu/gamma-1 synthesis in BCL1 subclones, we have analyzed mature and pre-RNA at the nascent and steady-state levels. We find mu and gamma-1 sequences linked in pre-RNA. However, the primary mu and gamma-1 transcription units are about the same length (almost-equal-to 15 kilobases). Initiation of gamma-1 pre-RNA occurs upstream of C-gamma-1 at sites identical to those seen in lipopolysaccharide/interleukin-4-induced normal B cells. We propose that dual mu/gamma-1 RNA synthesis occurs by a discontinuous transcription mechanism involving either trans-splicing or ligation of mu-pre-RNA initiated 5' of the variable-diversity-joining region to gamma-1 pre-RNA initiated 5' of C-gamma-1.