Expression of Iμ-Cγ hybrid germline transcripts subsequent to immunoglobulin heavy chain class switching

• Published in: International immunology 1994-04, Vol.6 (4), p.491-497
• Main Authors: Li, Suzanne C., Rothman, Paul B., Zhang, Jue, Chan, Christina, Hirsh, David, Alt, Frederick W.
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocyte Subsets; Base Sequence; Biological and medical sciences; Cell Line, Transformed; class switching; Fundamental and applied biological sciences. Psychology; Gene Expression - genetics; Genes, Switch - genetics; Genic rearrangement. Recombination. Transposable element; heavy chain; immunoglobulin; Immunoglobulin Class Switching - physiology; Immunoglobulin G - genetics; Immunoglobulin Heavy Chains - biosynthesis; Immunoglobulin Heavy Chains - genetics; Immunoglobulin M - genetics; Mice; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Polymerase Chain Reaction - methods; Spleen - cytology; Transcription, Genetic - physiology
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/6.4.491

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 - Cμ gene to particular downstream CH genes appears to be regulated by a process that involves mltogen and/or cytokine induction of germline CH transcripts from the downstream genes. We have examined the expression of germline Cμ transcripts (Iμ-Cμ transcripts) in splenic B cells and pre-B cell lines after cytokine and mltogen stimulation. In contrast to the expression of the germline transcripts from downstream CH genes, expression of germline Cμ transcripts was constitutive and unaffected by mltogen and cytokine treatment. After a primary switch recombination event, the germline Iμ 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 Iμ exon spliced to the CH exons of the switched CH gene. We discuss the potential role of the expression of hybrid Iμ-contalning transcripts in the class switch process. We also describe a novel and sensitive assay, based on the detection of the hybrid Iμ-contalnlng transcripts, that allows detection of class switch recombination events even in heterogeneous populations of cells.