IMMUNOGLOBULIN HEAVY-CHAIN GERM-LINE J(H)-C-MU TRANSCRIPTION IN HUMAN PRECURSOR B-LYMPHOCYTES INITIATES IN A UNIQUE REGION UPSTREAM OF DQ52

From human precursor B cells which had both immunoglobulin (Ig) heavy (H) chain loci in germ-line configuration, various IgH chain germ-line transcripts were isolated and sequenced. These transcripts were shown to contain sequences derived from the J(H) region, the IgH chain enhancer element or the Ig switch region. A number of isolated cDNA clones contained sequences at their 5' end that were derived from a single exon located just upstream of DQ52, designated the mu(o') element. Sequence analysis of a 920-bp genomic DNA segment, containing the mu(o') exon and its 5' flanking region, revealed the presence of various conserved motifs for DNA-binding proteins, such as E2A, Ets, NF-chi B and AP-2, which have previously been found in the IgH and L chain enhancers. We propose that the activity of the mu(o') element, resulting in germ-line transcription of the DQ52-J(H) gene segment, is required to generate full accessibility for the V(D)J recombinase.