Structure of TGF-β1-induced human immunoglobulin Cα1 and Cα2 germ-line transcripts

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Abstract
We have characterized the structure of the human immunoglobulln Cα1 and Cα2 germ-line transcripts that are synthesized upon treatment of human B lymphocytes with Branhamella catarrhalls (a B cell mitogen) and transforming growth factor β1 (TGF-β1). These transcripts initiate upstream of the switch α1 and switch α2 regions and contain, together with the Cα1 and Cα2 sequences, additional exons designated according to the generally accepted nomenclature Iα1 and Iα2 respectively. The lα exons are spliced directly onto the acceptor splice site of the CH1 domains of the Cα1 and Cα2 genes. As In other previously characterized germ-line transcripts, stop codons present in all three reading frames prevent translation of the Cα1 and Cα2 heavy-chain coding sequences. The longest open reading frame (ORF) present in the I exons can code for a polypeptide of only 26 amino acids. The human lα exons do not show any significant sequence homology with the corresponding mouse lα exon. However, comparison of nucleotide sequences of the genomic mouse and human lα regions demonstrated the presence of an -300 bp highly conserved element located immediately upstream of the transcription Initiation sites of the human and mouse Cα germ-line transcripts. The Isolation of the Cα1 and Cα2 germ-line transcripts will further facilitate the characterization of the molecular events responsible for the regulation of the human Cαheavy chain loci.

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