Cloning of a human immunoglobulin gene fragment containing both VH-D and D-JH rearrangements: implication for VH-D as an intermediate to VH-D-JH formation.

In an Epstein-Barr virus-transformed human B cell line we found an unusual immunoglobulin heavy chain gene rearrangement. Restriction mapping and sequencing analysis led us to conclude that VH-D and D-JH recombination took place in a single allele. Both VH-D and D-JH complexes still had their recombination signal sequences adjacent and the DNA sandwiched by these two complexes retained a germ-line configuration, suggesting the potential for a secondary rearrangement resulting in a VH-D(-D)-JH formation. With this finding, we propose a novel pathway, in which the VH-D complex is an intermediate in the formation of a functional VH exon.