Structure of Germline Immunoglobulin Heavy-Chain γ1 Transcripts in Interleukin 4 Treated Mouse Spleen Cells

Antibody class switching is mediated by a DNA recombination event that replaces the Cμ gene with one of the other heavy (H) chain constant region (C(H)) genes located 3' to the Cμ gene. The regulation of this process is essential to the immune response because different C(H) regions provide different biological functions. Correlative evidence indicates that the isotype (class) specificity of the switch is determined by the accessibility of specific C(H) genes as indicated by hypomethylation and transcriptional activity. For example, RNAs transcribed from specific unrearranged C(H) genes are induced prior to switching under conditions that promote subsequent switching to these same C(H) genes. The function of transcription of these germline C(H) genes is unknown. In this report, we describe the structure of RNA transcribed from unrearranged γ1 genes in mouse spleen cells treated with LPS plus .a HeLa cell supernatant containing recombinant interleukin 4. The germline γl RNA is initiated at multiple start sites 5' to the tandem repeats of the γ1 switch (Sγ1) region. As is true for analogous RNAs transcribed from unrearranged γ2b and c genes, the germline γ1 RNA has an exon transcribed from the region 5' to Sγ1 sequences, which is spliced at a unique site to the Cr gene. The germline γ1 RNA has an open-reading frame (ORF) that potentially encodes a small protein 48 amino acid in length.