Immunoglobulin genes in autoimmunity.

Abstract

The contribution of V germline genes and somatic mutation as well as the mechanism governing expression of the various V family genes in response to self-antigens are still unknown. Thus, we are still far from understanding the contribution and role of the B cell repertoire in human autoimmunity. Much of our current data on autoantibody gene repertoire are derived from laboratory generated hybridomas or animal model of autoimmune diseases. These may not reflect the human situation. In contrast, very few human autoantibodies with defined specificities have been structurally and genetically analyzed. In the future, meaningful data, perhaps from direct cloning and sequencing of autoantibodies derived from patients with autoimmune diseases, will be necessary to resolve issues in autoantibody repertoire usage. In this article, the prominent features of the human Ig repertoire, the usage of germline genes in autoantibodies, identifications of somatic mutations among autoantibodies and current data supporting either restricted or nonrestricted Ig gene usage and idiotypic expression among autoantibodies in several well-studied autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis are discussed.