RNA SPLICING GENERATES ALTERNATE FORMS OF GERMLINE IMMUNOGLOBULIN-ALPHA 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 alpha heavy chain transcript expressed in the murine B cell lymphoma 1.29-mu, a cell line that switches to lgA in culture, have been used to characterize the germline alpha transcription unit. The 5' end of these transcripts are heterogeneous, being derived from an exon denoted I-alpha located approximately 2.2 kb 5' of the alpha switch region. Sequence analysis of cDNA and genomic clones reveals that alternate splice donor sites generate I-alpha exons of varying length. While the two smaller spliced forms of I-alpha contain stop codons in the open reading frame of the C-alpha 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-alpha exon are fused to the C-alpha domain.