Evolution of antibody class switching: identification and transcriptional control of an Inu exon in the duck (Anas platyrhynchos).

Immunoglobulin class switching is characteristic to the tetrapod lineage, but the nature of this process has been elucidated only in mammals, where I-exon transcription initiates and directs the recombination in the IgH locus. Here, it is shown that an I-exon occurs 5' of the nu (IgY constant region) gene of the duck (Anas platyrhynchos): it is longer than mammalian I-exons and comprised primarily of tandem repeats. The Inu promoter was identified and shown to be responsive to stimulation with IL-4 but not LPS. It contains Oct, LYF-1, ATF, and C/EBP motifs. Site directed mutagenesis indicates that 2 C/EBP motifs are uniquely necessary for the response of the promoter to IL-4, as tested in the mouse pre-B cell line, 70Z/3. These results support the conclusion that the signal transduction pathways controlling I-exon promoter responses to cytokines have been highly conserved in vertebrate evolution.