Human cord blood antibody repertoire. Mixed population of VH gene segments and CDR3 distribution in the expressed C alpha and C gamma repertoires.

Abstract

Developmental regulation of the diversity of the antibody repertoire is associated with the controlled stepwise acquisition of Ag responsiveness during ontogeny. The development of IgG and IgA serum levels in humans lags far behind the maturation of the rest of the immune response. We cloned cord blood mononuclear cell C gamma and C alpha transcripts and compared them with a large database of > 250 published and unpublished sequences, including C mu transcripts from this same cord blood cDNA library, to determine whether restrictions in the expressed antibody repertoire contributed to the limitations of the neonatal IgG and IgA response. We found a diverse antibody repertoire containing a high frequency of the same VH gene segments first identified in fetal liver, as well as VH elements homologous to those in the cord blood C mu transcripts. Although VH, DH, and JH utilization differed, the distribution of CDR3 lengths in the C gamma transcripts was similar to that found in fetal liver C mu transcripts, whereas the distribution of CDR3 lengths in the C alpha transcripts was similar to that found in cord blood C mu. This comprehensive analysis of the C mu, C gamma, and C alpha V domain repertoires provides new insights into our understanding of the timing of sequential B cell waves that seed peripheral lymphoid compartments during development.