Molecular cloning of translocations involving chromosome 15 and the immunoglobulin C alpha gene from chromosome 12 in two murine plasmacytomas.

Abstract

Expression of IgA by plasmacytomas occurs as a result of a DNA rearrangement that brings the variable region gene, VH, a few kilobases 5' to the constant region gene, C alpha. In this study, we show that the allelic nonexpressed C alpha gene also is rearranged in most plasmacytomas. Cloning, restriction mapping, heteroduplex analyses, and sequence analyses of the nonproductively rearrange C alpha genes from two plasmacytomas, M603 and M167, have demonstrated that the nonproductive rearrangement occurs within the alpha switching region, S alpha. In each case, the same DNA sequence has been joined to the 5' side of C alpha and we have termed this DNA "NIRD" (for nonimmunoglobulin rearranged DNA). Southern blotting analyses of genomic DNAs from various IgG-, IgM-, or IgA-producing plasmacytomas suggest that NIRD is rearranged in almost all plasmacytomas. However, NIRD rearranges to the S alpha region only in IgA-producing cells, not in IgM or IgG producers. Cytogenetic evidence has shown that T(12;15) translocations are common in murine plasmacytomas. Immunoglobulin heavy chain genes are located on chromosome 12, and the translocation breakpoint in plasmacytomas occurs near the immunoglobulin genes. NIRD has been mapped to chromosome 15 by Southern blotting analysis of mouse-hamster cell lines, suggesting that the nonproductively rearranged C alpha clones represent the T(12;15) translocations identified cytogenetically. Therefore, we have identified a region of DNA on chromosome 15 that is commonly rearranged in transformed mouse lymphocytes. We speculate on the significance of NIRD in neoplastic transformation of mouse lymphocytes.