IFN-γ represses ε germline transcription and subsequently down-regulates switch recombination to ε

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Abstract
Cytoklnes have the ability to regulate the isotypes of antibodies produced during an Immune response. For instance, IL-4 has been shown to induce the production of IgE by B cells, while IFN-γ has been shown to inhibit this induction. Recent work has revealed that IL-4 appears to induce class switching to εthrough Its ability to specifically induce germline ε transcripts. Germline εtranscription appears to target class-switch recombination to the εlocus. However, the mechanism by which IFN-γ Inhibits the IL-4 induction of IgE is unknown. We hypothesized that IFN-γ and IL-4 may have antagonistic effects on the same stage of B cell differentiation. Northern blotting analyses show that IFN-γ suppresses the IL-4 Induction of germline εtranscripts. In transient transfection assays, the IL-4 Induction of transcription Imparted by the minimal 179 bp germline εpromoter Is repressed by IFN-γ. Utilizing a digestion circularization -polymerase chain reaction assay we show that IL-4 Induces switch recombination to ε, while IFN-γ suppresses switch recombination to ε. These studies support a model that, through their differential effects on a cis-controlllng element that regulates germline εtranscription, IL-4 and IFN-γ are able to modulate B cell switch recombination to εin a coordinated manner.

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