Expression of I mu-C gamma hybrid germline transcripts subsequent to immunoglobulin heavy chain class switching.
Germline CH transcripts initiate from a non-coding I exon and terminate downstream of the associated CH exons. Ig heavy chain class switch recombination from the VDJ-C mu gene to particular downstream CH genes appears to be regulated by a process that involves mitogen and/or cytokine induction of germline CH transcripts from the downstream genes. We have examined the expression of germline C mu transcripts (I mu-C mu transcripts) in splenic B cells and pre-B cell lines after cytokine and mitogen stimulation. In contrast to the expression of the germline transcripts from downstream CH genes, expression of germline C mu transcripts was constitutive and unaffected by mitogen and cytokine treatment. After a primary switch recombination event, the germline I mu promoter, which is now associated with a downstream CH gene, continues to be active--leading to the generation of a novel germline transcript consisting of the I mu exon spliced to the CH exons of the switched CH gene. We discuss the potential role of the expression of hybrid I mu-containing transcripts in the class switch process. We also describe a novel and sensitive assay, based on the detection of the hybrid I mu-containing transcripts, that allows detection of class switch recombination events even in heterogeneous populations of cells.
Howard Hughes Medical Institute, Boston, MA.
S C
SC
Li
P B
PB
Rothman
J
J
Zhang
C
C
Chan
D
D
Hirsh
F W
FW
Alt
D000818:Animals; D016175:B-Lymphocyte Subsets; D001483:Base Sequence; D002461:Cell Line, Transformed; D015870:Gene Expression / Q000235:genetics; D005812:Genes, Switch / Q000235:genetics; D017578:Immunoglobulin Class Switching / Q000502:physiology*; D007074:Immunoglobulin G / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D013154:Spleen / Q000166:cytology; D014158:Transcription, Genetic / Q000502:physiology*
D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M