Autoantibodies: the search for origins, target autoantigens and pathogenicity

The origins of autoantibodies remain largely unknown. Burnet suggested that self-reactive clones of B lymphocytes are deleted during ontogeny and that 'forbidden' clones of autoantibody-producing B lymphocytes arise as a consequence of somatic mutation of the variable regions of immunoglobulin genes. The alternative view, which is gaining increasing support, is that autoreactive B cells are present in all normal individuals but are held in check by control mechanisms, e.g. by the idiotypic network of Jerne. Autoantibodies segregate with clusters of autoimmune diseases and are useful diagnostic markers of these diseases. The autoantigens targeted by these autoantibodies are largely unknown. The precise molecular characteristics of these autoantigens are currently under active investigation by immunochemical and recombinant DNA methods. Precise definition of these autoepitopes should lead to sensitive immunoassays and studies directed at determining the pathogenicity of the autoantigens. The new knowledge gained in this way may lead to successful restoration of tolerance to self antigens.