Novel rearrangements at the immunoglobulin D locus. Inversions and fusions add to IgH somatic diversity.
IgH rearrangements (VH-D, D-JH) are central to the generation of antibody diversity. The majority of the diversity seen in the third hypervariable region is generated by the D segment and at the joints formed by both junctional and N segment variation during D-JH and VH-D rearrangements. The mechanisms that regulate rearrangement are thought to obey the 12/23 rule, wherein D-D or VH-JH rearrangements are precluded. Here, we present evidence that D-D fusions do in fact occur, either as direct or inverted rearrangements. The fused D segments so generated may be fully capable of proceeding in subsequent D-JH and VH-D rearrangements. The resultant VH-D-D-JH recombinations add another dimension to the potential repertoire of IgH V regions by increasing the level of combinatorial diversity and by providing additional sites for N region variation.
Meek
K D
KD
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Hasemann
C A
CA
Capra
J D
JD
D000818:Animals; D000916:Antibody Diversity; D001483:Base Sequence; D015139:Blotting, Southern; D001853:Bone Marrow / Q000276:immunology; D007446:Chromosome Inversion; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D007072:Immunoglobulin D / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes
D007072:Immunoglobulin D; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D015345:Oligonucleotide Probes; D004247:DNA