STRUCTURE AND EXPRESSION OF HUMAN GERMLINE VH TRANSCRIPTS

The human V(H)5 family consists of two functional genes and one pseudogene. We have found a novel 1.2-kb V(H)5 gene transcript in normal fetal liver and cord blood and in transformed B lineage cells. V(H)5-positive cDNA clones were isolated from precursor B acute lymphoblastic leukemia, B chronic lymphoblastic leukemia, Epstein-Barr Virus-transformed B cell lines, and cord blood, and were identified as transcripts of unrearranged V(H)5 genes (germline transcripts). The cDNA clones were derived from both functional and pseudo-V(H)5 genes. Most germline transcripts appear to initiate at the normal V(H) promoter and are cleaved and polyadenylated at sites several hundred bases downstream of the V(H)5 coding region. Correct splicing of the leader intron was observed in all clones. In functional and pseudo-V(H)5 cDNAs, an open translational reading frame extends from the leader to a termination codon in the nonamer. Only limited polymorphisms were observed in the coding as well as flanking regions of the V(H)5 transcripts. Functional and pseudo-V(H)5 cDNAs are also highly homologous throughout. The many similarities between human germline V(H)5 transcripts and previously identified murine germline V(H)J558 transcripts are discussed.