The human cord blood antibody repertoire. Frequent usage of the V_H7 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_μ⁺ transcripts. We found this set of transcripts to be enriched for J_H4, 5 and 6, whereas previously reported fetal transcripts preferentially expressed J_H3 and 4. The cord blood transcripts used a number of different D_H gene segments, whereas fetal transcripts were enriched for D_HQ52. Of the thirteen cord blood sequenced, three were members of the newly described V_H7 family which to date has not been detected in fetal liver. Indeed, only one of the isolated V_H gene segments had 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.