Structural analyses of human developmentally regulated Vh3 genes.

In mice, a restricted set of the Jh-proximal Vh genes are preferentially expressed during early ontogeny. Recently, analyses of human Ig cDNA from a fetal liver revealed a restricted set of Vh genes which belong to the Vh1, 3, 4, and 6 families. Although the Vh6 and some Vh5 genes are proximal to the Jh region, no Vh5 gene was found in the fetal liver, suggesting that the distance between the Jh genes and some early-expressed Vh genes may not be the only factor responsible for Vh gene expression during early development. As an initial step in searching for other underlying mechanisms, we characterized two human germline Vh3 genes which belong to the developmentally restricted Vh repertoire, and found that they contain many enhancer-like sequences which are identical, or highly homologous to, various transcriptional enhancer motifs. Hence, it is conceivable that, in addition to the established positional effects, cis regulatory elements may be important in the programmed expression of some Vh genes during early B-lymphocyte development.