Synthesis of germ-line γ1 immunoglobulin heavy-chain transcripts in resting B cells: Induction by interleukin 4 and inhibition by interferon γ

Interleukin 4 (IL-4) induces the expression of IgG1 and IgE in lipopolysaccharide-stimulated B cells. Previous studies have suggested that heavy-chain class switching may be regulated by increasing the accessibility of specific switch regions to switch recombinases. In this study, we have used an RNase protection assay to demonstrate that IL-4 induces expression of germ-line γ1 transcripts in B cells within 4 hr of culture; induction is dose-dependent and is inhibited by interferon γ. IL-4 alone is capable of inducing the expression of germ-line γ1 transcripts in small, resting B cells, but lipopolysaccharide enhances expression. The germ-line transcripts are the same size (1.8 and 3.4 kilobases) as the secreted and membrane forms of the functional γl mRNAs and presumably result from the splicing of an upstream switch-region exon(s) to the γl constant-region exon(s). These data strongly support the 'accessibility' model for the regulation of isotype switching and suggests that lymphokines such as IL-4 may direct specific switch events by transcriptional activation of the corresponding switch regions.