The human VH repertoire: a restricted set of VH genes may be the target of immune regulation.

During the development of the immune system, a restricted set of VH gene segments provides the bulk of the immunoglobulin heavy chain repertoire. Most of these VH genes have been found later in life encoding autospecificities either in normals or in patients with autoimmune diseases. Additionally, there is considerable evidence that the fetal/neonatal B-cell repertoire is autoreactive and idiotypically connected. In the course of sequencing the heavy chain of a panel of human autoantibodies mainly derived from patients with autoimmune diseases, we found that one of the VH families, and more specifically one single VH gene contributes to a large extent to the adult autoimmune repertoire in restricted as well as unrestricted responses. This VH gene segment is not particularly overexpressed in the fetus. Since the only common element to these autoreactive responses is the region encoded by the VH gene itself, these observations may provide an important insight into B-cell regulation.