Structure and expression of mouse germline immunoglobulin γ3 heavy chain transcripts induced by the mitogen lipopolysaccharide

Publisher Website
Google Scholar
Abstract
Germline immunoglobulin heavy chain gene transcription is though to direct isotype switching by modulating the accessibility of specific switch regions to a recombinase. In this study, cloned cDNA copies of mouse germlineIgh-8 RNAs have been used to characterize theIgh-8 transcription unit. The 5' end of these transcripts are derived from an exon denotedIg3, located 1 kilobase 5' of theIgh-8 switch region. Sequence analysis of cDNA and genomic clones reveals that these RNAs are noncoding. In splenic B cell cultures treated with lipopolysaccharide (LPS), germlineIgh-8 transcript levels are upregulated after 8 h due to increased transcription. This induction is consistent with the identification of a putative binding site for the LPS inducible transcription factor NF-gkB approximately 150 nucleotides upstream of the sites of transcript initiation. Furthermore, nucleotide sequence comparisons reveal that the region encompassing the site of germlineIgh-8 transcription initiation is highly homologous to part of the Ig2b exon, and is also conserved upstream of the Igh-1 switch region. The implications of these findings for the control of germlineIgh-8 transcription is discussed.