Structure and Expression of Germ Line Immunoglobulin Heavy-Chain ε Transcripts: Interleukin-4 Plus Lipopolysaccharide-Directed Switching to Cε

Abstract

We have isolated cDNA clones complementary to a truncated immunoglobulin heavy-chain Cε RNA transcript previously found to be induced in B lymphoid cells by treatment with lipopolysaccharide (LPS) combined with interleukin-4 (IL-4). We demonstrate that this transcript initiates from a promoter upstream of the germ line ε class-switch recombination region (Se region). The major germ line Cε transcript contains a small 5' exon contributed by sequences upstream of the Sε region spliced to the normal Ce exons. Treatment of splenic B lymphoid cells with LPS plus IL-4 induces the expression of transcripts from the germ line ε transcription unit followed by expression of normal immunoglobulin ε heavy-chain mRNA. Furthermore, we demonstrate that similar treatment of transformed precursor B cell lines induces the expression of germ line ε transcripts followed by class switching to ε expression in these lines. This is the first demonstration of switching to ε in cells of the pre-B stage. The general structure of the germ line ε transcript and transcription unit is similar to that previously characterized for germ line γ2b transcripts. However, expression of these two germ line transcription units in B-lineage cells is inversely regulated by IL-4 (plus LPS) treatment, correlating with the effects of these treatments on switching to these loci.