Physical linkage of a variable region segment and the joining region segment of the human immunoglobulin heavy chain locus.

We have isolated overlapping cosmid clones containing both human VH-VI and D gene segments from genomic libraries of a human lymphocyte line which has the germline context of the immunoglobulin loci. Characterization of the cosmid clones revealed that the VH-VI gene was located about 20 kb upstream to the D4 segment with the same transcriptional orientation relative to the D and JH segments. No other VH genes were found downstream to the VH-VI gene using VH probes hybridizing all the six human VH families so far identified. The results indicate that the VH-VI gene is the most proximal VH segments among the known VH family members and that the distance between the VH and JH segments is not longer than 70 kb in the human genome.