The diversity gene segments (DH) of the immunoglobulin heavy chain have been shown to be important in antigen recognition and idiotype expression. Preliminary results indicate that the somatic human DH repertoire is highly diversified probably by the contribution of numerous germ line (GL) DH genes and somatic mechanisms such as gene conversion, DH-DH fusions and utilization of the reverse complementary sequence of GL genes. Our long-term goal is to assess the actual diversity of the human DH repertoire and to elucidate the genetic mechanisms involved in the generation of diversity. We will also address the question as to whether or not the utilization of these mechanisms and expression of specific DH repertoires is developmentally regulated. In order to accomplish these goals DH-specific cDNA libraries from embryonic, neonatal and adult B cells will be analyzed. We will investigate the contribution of GL DH genes in different ways including novel approaches for the localization, cloning and sequencing of new GL DH genes.
