Non-Immunoglobulin-Associated DNA Rearrangements in Mouse Plasmacytomas

We have characterized a class of DNA rearrangements in plasmacytomas. These recombination events involve a DNA sequence whose origin is outside of the locus of the heavy chain constant region genes, CH. Therefore, we choose to refer to this sequence as non-immunoglobulin-associated rearranging DNA (NIARD). We have isolated two abortively rearranged Cαgenes, generated by NIARD events from the α -producing J558 myeloma. Restriction endonuclease maps of these sequences reveal two possible recombination sites in NIARD that are separated by ≈ 6.5 kilobase pairs of DNA (defined as 5′and 3′sites). A NIARD rearrangement occurs in 15 out of 20 plasmacytomas tested, including γ 3-, γ 1-, γ 2b-, γ 2a-, and α -producers, but this event usually does not involve a CHswitch (S) region. In fact, only Sαappears to accept NIARD. However, NIARD did not undergo a rearrangement in eight IgA-producing hybridomas tested. One germ-line copy of NIARD (a 22-kilobase pair EcoRI fragment) is retained in all plasmacytomas. NIARD does not appear to possess repetitive DNA sequences homologous to Sμor Sα. We discuss the possible role and implications of NIARD-like sequence rearrangements in allelic exclusion and chromosomal translocation events in plasmacytomas.