Nonhomologous recombination at sites within the mouse JH-C delta locus accompanies C mu deletion and switch to immunoglobulin D secretion.
Plasma cells secrete immunoglobulins other than immunoglobulin M (IgM) after a deletion and recombination in which a portion of the immunoglobulin heavy-chain locus (IgH), from the 5'-flanking region of the mu constant-region gene (C mu) to the 5'-flanking region of the secreted heavy-chain constant-region gene (CH), is deleted. The recombination step is believed to be targeted via switch regions, stretches of repetitive DNA which lie in the 5' flank of all CH genes except delta. Although serum levels of IgD are very low, particularly in the mouse, IgD-secreting plasmacytomas of BALB/c and C57BL/6 mice are known. In an earlier study of two BALB/c IgD-secreting hybridomas, we reported that both had deleted the C mu gene, and we concluded that this deletion was common in the normal generation of IgD-secreting cells. To learn how such switch recombinations occur in the absence of a switch region upstream of the C delta 1 exon, we isolated seven more BALB/c and two C57BL/6 IgD-secreting hybridomas. We determined the DNA sequences of the switch recombination junctions in eight of these hybridomas as well as that of the C57BL/6 hybridoma B1-8. delta 1 and of the BALB/c, IgD-secreting plasmacytoma TEPC 1033. All of the lines had deleted the C mu gene, and three had deleted the C delta 1 exon in the switch recombination event. The delta switch recombination junction sequences were similar to those of published productive switch recombinations occurring 5' to other heavy-chain genes, suggesting that nonhomologous, illegitimate recombination is utilized whenever the heavy-chain switch region is involved in recombination.
Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892.
J D
JD
Owens
F D
FD
Finkelman
J D
JD
Mountz
J F
JF
Mushinski
D000818:Animals; D001483:Base Sequence; D002872:Chromosome Deletion; D015342:DNA Probes; D005803:Genes, Immunoglobulin; D006825:Hybridomas / Q000276:immunology; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007072:Immunoglobulin D / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007134:Immunoglobulin Switch Region; D007138:Immunoglobulin delta-Chains / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D015183:Restriction Mapping
D015342:DNA Probes; D007127:Immunoglobulin Constant Regions; D007072:Immunoglobulin D; D007143:Immunoglobulin Heavy Chains; D007138:Immunoglobulin delta-Chains; D007148:Immunoglobulin mu-Chains; D009841:Oligonucleotides