Coexpression of mu and gamma 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 (approximately 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.
Nolan-Willard
M
M
University of Texas Southwestern Medical Center, Department of Microbiology, Dallas 75235.
Berton
M T
MT
Tucker
P
P
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D005786:Gene Expression Regulation; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D007132:Immunoglobulin Isotypes / Q000235:genetics; D007142:Immunoglobulin gamma-Chains / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D015448:Leukemia, B-Cell / Q000235:genetics; D051379:Mice; D009694:Nucleic Acid Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D007132:Immunoglobulin Isotypes; D007142:Immunoglobulin gamma-Chains; D007148:Immunoglobulin mu-Chains; D009694:Nucleic Acid Precursors; D012333:RNA, Messenger; D012321:DNA-Directed RNA Polymerases