A MAP OF THE HUMAN-IMMUNOGLOBULIN V-H LOCUS COMPLETED BY ANALYSIS OF THE TELOMERIC REGION OF CHROMOSOME 14Q

Analysis of the telomeric region of chromosome 14q has enabled us to complete a map of the immunoglobulin V-H locus which accounts for almost all V-H segments known to rearrange in B-lymphocytes. The human germline V-H repertoire consists of approximately 50 functional V-H segments - the exact number depending on the haplotype - spanning 1,100 kilobases upstream of the J(H) segments. A yeast artificial chromosome used to map these segments was isolated by its ability to provide telomere activity in yeast, suggesting that the V-H locus may be located within a few kilobases of the 14q telomere. The limited structural diversity encoded by the functional V-H segments demonstrates the importance of combinatorial diversity produced by VDJ joining and the association of heavy and light chains in producing the human antibody repertoire.