Rearrangement of a VH-associated LINE-1 element with the expressed IgH cluster in a murine myeloma cell line

Abstract

The MPC11 mouse myeloma cell line (IgG2b kappa) has yielded numerous variants in Ig heavy-chain production. One such variant, E5.7A14, fails to produce gamma 2b heavy chain but still produces kappa light chain. Comparison of the restriction maps of E5.7A14 and MPC11 has shown that in E5.7A14, the expressed MPC11VH gene has been deleted and replaced by a different DNA segment. Cloning and sequencing of the rearranged heavy-chain gene has identified the new DNA segment as a virtually full-length LINE-1 element that, in germ line, apparently lies in a inverted transcriptional orientation downstream of a previously unknown member (pseudogene) of the VH3609 gene family. The LINE-1 rearrangement was associated with an inversion of a 2-kb segment of the J-C gamma 2b intron and a deletion of switch sequences. The nature of the rearrangements and the sequences at recombination and inversion breakpoints suggest that the rearrangement event was mediated via class switch mechanisms. This is one of a limited number of reports that both characterizes a LINE rearrangement and localizes the germ-line origin of the particular LINE element involved.