THE HUMAN CORD BLOOD ANTIBODY REPERTOIRE - FREQUENT USAGE OF THE VH7 GENE FAMILY

We have previously demonstrated a consistent preferential usage of a small set of V(H), D(H) and J(H) gene segments in second-trimester fetal liver. To examine the extent of heavy chain repertoire diversification in newborns, we generated an unrestricted cDNA library from cord blood mononuclear cells and sequenced the variable domains of randomly isolated C(mu)+ transcripts. We found this set of transcripts to be enriched for J(H)4, 5 and 6, whereas previously reported fetal transcripts preferentially expressed J(H)3 and 4. The cord blood transcripts used a number of different D(H) gene segments, whereas fetal transcripts were enriched for DHQ52. Of the thirteen cord blood sequenced, three were members of the newly described V(H)7 family which to date has not been previously observed in fetal transcripts. As a result of enhanced N-region addition and use of longer D(H) and J(H) gene segments, both the sequence diversity and range of potential antigen-binding structures of cord blood complementarity-determining region 3 domains was vastly expanded. Thus, the repertoire bias evident in fetal liver was no longer apparent in this more mature population of cord blood B cells.