RNA splicing generates alternate forms of germline immunoglobulin α heavy chain transcripts

Emerging evidence implicates germline immunoglobulin heavy chain gene transcription in the targeting of heavy chain genes for switch recombination. In this study, cloned cDNA copies of the major germline α heavy chain transcript expressed in the murine B cell lymphoma l.29μ, a cell line that switches to IgA in culture, have been used to characterize the germline α transcription unit. The 5' end of these transcripts are heterogeneous, being derived from an exon denoted I_α located ̃2.2 kb 5' of the α switch region. Sequence analysis of cDNA and genomic clones reveals that alternate splice donor sites generate I_α exons of varying length. While the two smaller spliced forms of I_α contain stop codons in the open reading frame of the C_α gene, transcripts utilizing the 3' most splice donor signal may encode a protein in which amino acids derived from the 3' end of the I_α exon are fused to the C_α domain.