Spontaneous Deletions In Ig Heavy-Chain Genes - Flanking Sequences Influence Splice Site Selection

The cell line G403.4.7, isolated as a spontaneous variant of the MPC-11 derived myeloma G403.4, produces a truncated gamma-2b HC protein, but no light chain (LC), and a single gamma-2b specific transcript of 2.4kb. This gamma-2b transcript consists of the VDJ and C(H)1 exons, the C(H)1 to Hinge (Hi) intervening sequence (IVS) and Hi exon, part of the IVS between the two membrane exons M1 and M2, and most of the membrane 3' untranslated (UT) region. Even though the mature mRNA contains intronic sequences, it is abundant in the cytoplasm. Analysis of the gamma-2b genomic organization reveals that this unusual transcript results in part from two genomic deletions of 2.5kb and 588bp and in part from an altered splicing pattern. This altered splicing pattern is probably a consequence of the sequence alterations resulting from the genomic deletions. Analysis of these events provides some interesting insights into the mechanism of splice site selection and the evolution of introns and exons.