VHD rearrangements in human immunoglobulin heavy chain minilocus transgenic mice.
Typically, immunoglobulin VHDJH recombination is performed in two steps with D to JH rearrangement preceding VH to DJH rearrangement. Using a human immunoglobulin heavy chain transgenic minilocus, we previously demonstrated that a non-conventional human D gene segment termed DIR2 could be recombined to a VH gene segment to form VHD rearrangements. Here, we demonstrate that VHD rearrangements involve conventional D gene segments as well. VHD rearrangements are easily detected and are diverse. Similarly to DJH rearrangements, VHD rearrangements occur by deletion and inversion. They occur approximately 1000 times less frequently than DJH rearrangements. VHD rearrangements can constitute intermediates for the formation of VHDDJH rearrangements.
Tuaillon
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Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Capra
J D
JD
D000818:Animals; D000916:Antibody Diversity / Q000235:genetics*; D001483:Base Sequence; D015139:Blotting, Southern; D007446:Chromosome Inversion; D004254:DNA Nucleotidyltransferases / Q000378:metabolism*; D015322:Gene Rearrangement, B-Lymphocyte; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D005818:Genetic Engineering; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007134:Immunoglobulin Switch Region / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D016415:Sequence Alignment; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D045567:VDJ Recombinases
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases