Structure and expression of murine germ-line immunoglobulin epsilon heavy chain transcripts induced by interleukin 4.
The murine lymphokine, interleukin 4 (IL-4) is able to specifically promote isotype switching to IgG1 and IgE in cultures of mitogen-stimulated B cells. Emerging evidence suggests that germ-line immunoglobulin heavy chain gene transcription may direct switching by modulating switch-region accessibility to a recombinase. In this study, cloned cDNA copies of the germ-line epsilon heavy chain transcript have been used to determine the genomic organization of this transcription unit. The 5' end of these transcripts are derived from an exon, denoted I epsilon, located 2 kilobases 5' of the C epsilon switch region [C epsilon = epsilon heavy chain constant (C) region gene]. Nucleotide sequence analysis reveals that this RNA does not encode a protein, as the I epsilon exon contains termination codons in all reading frames. Germ-line epsilon chain transcripts can be detected in cultures of normal splenic B cells treated with IL-4 within 24 hr, and this expression correlates with subsequent switching to C epsilon. Consistent with the IL-4 inducibility of this RNA is the identification of a motif upstream from the site of transcription initiation that closely resembles a transcription element implicated in the IL-4 regulation of the gene encoding the murine class II histocompatibility antigen, A alpha k. These data lend support to the accessibility model of isotype switching and implicate IL-4 in the transcriptional activation of the C epsilon locus.
Gerondakis
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Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
D000818:Animals; D001402:B-Lymphocytes; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000235:genetics; D005803:Genes, Immunoglobulin / Q000187:drug effects*; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007073:Immunoglobulin E / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D015847:Interleukin-4 / Q000494:pharmacology*; D008223:Lymphoma; D051379:Mice; D008969:Molecular Sequence Data; D009710:Nucleotide Mapping; D012334:RNA, Neoplasm / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D015183:Restriction Mapping; D014158:Transcription, Genetic / Q000187:drug effects*
D004273:DNA, Neoplasm; D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E