Regulation of the antibody repertoire through control of HCDR3 diversity.

In man, as in mouse, diversification of the antibody repertoire appears to follow a strict developmental program whereby antigen specificities are serially acquired during ontogeny. When compared to the adult repertoire, the fetal antibody repertoire is highly enriched for polyreactive specificities of low affinity. Although the mechanisms governing the development of this fetal repertoire differ between human and mouse, the composition and structure of the fetal antibodies produced by both species are quite homologous. Specifically, both species use similar V gene segments and restrict the sequence and structure of the third complementarity determining region (HCDR3) of the antibody heavy chain. The precise role that this restriction of the HCDR3 might play in the development of immunocompetence in the human remains to be elucidated.