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 specificitie s are serially acquired during ontogeny. When compared to the adult re pertoire, the fetal antibody repertoire is highly enriched for polyrea ctive specificities of low affinity. Although the mechanisms governing the development of this fetal repertoire differ between human and mou se, the composition and structure of the fetal antibodies produced by both species are quite homologous. Specifically, both species use simi lar V gene segments and restrict the sequence and structure of the thi rd complementarity determining region (HCDR3) of the antibody heavy ch ain. The precise role that this restriction of the HCDR3 might play in the development of immunocompetence in the human remains to be elucid ated. (C) 1998 Elsevier Science Ltd. All rights reserved.