Novel rearrangements at the immunoglobulin D locus. Inversions and fusions add to IgH somatic diversity

Abstract

IgH rearrangements (V(H)-D, D-J(H)) 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-J(H) and V(H)-D rearrangements. The mechanisms that regulate rearrangement are thought to obey the 12/23 rule, wherein D-D or V(H)-J(H) 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-J(H) and V(H)-D rearrangements. The resultant V(H)-D-D-J(H) 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.