Stage-specific transcription of germline lgH C_γ and C_α regions during human B cell differentiation

Previous studies have suggested that transcription of germline heavy chain constant region (C_H)genes in murlne B cells may determine the potential of their different C_H regions to undergo isotype switch recombination. We have examined the transcriptional activity across the immunoglobulin heavy chain (IgH) locus in human B lineage cells. Transcription of germline C_γ and C_α was observed in every surface lgM+ or surface lgM+/lgD+ B cell stage cell line and malignancy. In contrast, such transcription could not be detected in pre-B cells and only low levels of C_α but not C_γ transcription were evident in IgM-secreting plasmablast cells. Transcriptional activity of germline IgH C_ε was singularly absent at all stages of B cell development. Our results suggest that germline transcription of the C_γ and C_α regions may be a constitutive feature of the human B cell differentiation program. Because this transcriptional activity is limited primarily to the B cell stage and occurs prior to the actual isotype switch, the induction of C_γ and C_α transcription may represent preparation of the downstream lgH chromatin for potential switch recombination.