Stage-specific transcription of germline IgH C gamma and C alpha regions during human B cell differentiation.
Previous studies have suggested that transcription of germline heavy chain constant region (CH) genes in murine B cells may determine the potential of their different CH 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 gamma and C alpha was observed in every surface IgM+ or surface IgM+/IgD+ 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 alpha but not C gamma transcription were evident in IgM-secreting plasmablast cells. Transcriptional activity of germline IgH C epsilon was singularly absent at all stages of B cell development. Our results suggest that germline transcription of the C gamma and C alpha 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 gamma and C alpha transcription may represent preparation of the downstream IgH chromatin for potential switch recombination.
Kerr
W G
WG
Division of Developmental and Clinical Immunology, University of Alabama, Birmingham 35294.
Burrows
P D
PD
D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D005803:Genes, Immunoglobulin; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007134:Immunoglobulin Switch Region; D007137:Immunoglobulin alpha-Chains / Q000235:genetics; D007142:Immunoglobulin gamma-Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology; D011995:Recombination, Genetic; D014158:Transcription, Genetic
D007127:Immunoglobulin Constant Regions; D007137:Immunoglobulin alpha-Chains; D007142:Immunoglobulin gamma-Chains