Coexpression of μ and γ1 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 μ and γ1 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 μ/γ1 synthesis in BCL₁ subclones, we have analyzed mature and pre-RNA at the nascent and steady-state levels. We find μ and γ1 sequences linked in pre-RNA. However, the primary μ and γ1transcription units are about the same length (≈15 kilobases). Initiation of γ1 pre-RNA occurs upstream of Cγ1 at sites identical to those seen in lipopolysaccharide/interieukin-4-induced normal B cells. We propose that dual μ/γ1 RNA synthesis occurs by a discontinuous transcription mechanism involving either trans-splicing or ligation of μ pre-RNA initiated 5′ of the variable-diversity-joining region to γ1 pre-RNA initiated 5′ of Cγ1.