Early Restriction of the Human Antibody Repertoire

Abstract

Diversification of the antibody repertoire in mammals results from a series of apparently random somatically propagated gene rearrangement and mutational events. Nevertheless, it is well known that the adult repertoire of antibody specificities is acquired in a developmentally programmed fashion. As previously shown, rearrangement of the gene segments encoding the heavy-chain variable regions (V H ) of mouse antibodies is also developmentally ordered: the number of V H gene segments rearranged in B lymphocytes of fetal mice is small but increases progressively after birth. In this report, human fetal B-lineage cells were also shown to rearrange a highly restricted set of V H gene segments. In a sample of heavy-chain transcripts from a 130-day human fetus the most frequently expressed human V H element proved to be closely related to the V H element most frequently expressed in murine fetal B-lineage cells. These observations are important in understanding the development of immunocompetence.