The human cord blood antibody repertoire. Frequent usage of the V_H7 gene family

Abstract

We have previously demonstrated a consistent preferential usage of a small set of VH, DH and JH 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 Cmu+ transcripts. We found this set of transcripts to be enriched for JH4, 5 and 6, whereas previously reported fetal transcripts preferentially expressed JH3 and 4. The cord blood transcripts used a number of different DH gene segments, whereas fetal transcripts were enriched for DHQ52. Of the thirteen cord blood sequenced, three were members of the newly described VH7 family which to date has not been detected in fetal liver. Indeed, only one of the isolated VH gene segments had been previously observed in fetal transcripts. As a result of enhanced N-region addition and use of longer DH and JH 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.