Physical linkage of a human immunoglobulin heavy chain variable region gene segment to diversity and joining region elements.

Antibody genes are assembled from a series of germ-line gene segments that are juxtaposed during the maturation of B lymphocytes. Although diversification of the adult antibody repertoire results in large part from the combinatorial joining of these gene segments, a restricted set of antibody heavy chain variable (VH), diversity (DH), and joining (JH) region gene segments appears preferentially in the human fetal repertoire. We report here that one of these early-expressed VH elements (termed VH6) is the most 3' VH gene segment, positioned 77 kilobases on the 5' side of the JH locus and immediately adjacent to a set of previously described DH sequences. In addition to providing a physical map linking human VH, DH, and JH elements, these results support the view that the programmed development of the antibody VH repertoire is determined in part by the chromosomal position of these gene segments.