Transcriptional regulation of the germline immunoglobulin C alpha and C epsilon genes: implications for commitment to an isotype switch.
Lymphokine directed isotype switching is preceded by the induced expression of the corresponding germline Ig heavy chain constant region (CH) gene. This association favors a model in which lymphokine induced germline CH gene expression promotes switch recombination by increasing the accessibility of the switch region to a recombinase(s). An important prediction of this model is that the induction of germline CH RNAs represents increased specific de novo transcription. To test if this prediction is fulfilled by the switch commitment factors, IL-4 and transforming growth factor-beta (TGF-beta), we have utilized a B cell line, 1.29, that switches from IgM to IgE and IgA in vitro. In this cell line, IL-4 and TGF-beta increase germline C epsilon and C alpha RNA levels respectively, predominantly by elevating transcription of these genes. Transcription of germline C epsilon and C alpha genes appears to be independently regulated and is not affected by lipopolysaccharide or IL-5. These results are discussed in the context of the molecular events necessary to commit a B cell to an isotype switch.
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
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Gaff
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Grumont
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Gerondakis
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D005803:Genes, Immunoglobulin; D005812:Genes, Switch; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007132:Immunoglobulin Isotypes / Q000235:genetics*; D007134:Immunoglobulin Switch Region; D015847:Interleukin-4 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D008070:Lipopolysaccharides; D051379:Mice; D008954:Models, Biological; D011061:Poly A / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D015848:Interleukin-5; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D011061:Poly A