[Molecular genetic analysis of autoantibody production in systemic lupus erythematosus]

This review summarizes studies from our and other laboratories attempting to define the molecular and clonotypic origin of autoantibodies that typify systemic autoimmune diseases such as lupus and rheumatoid arthritis. Comparative restriction fragment length polymorphism (RFLP) studies investigating the immunoglobulin (Ig) germline gene organization in lupus-prone strains of mice suggested that the disease can develop in different Ig heavy (H) and light (L) chain haplotypes, and that the Ig germline genes in lupus mice are probably normal. Analysis of the Ig gene segments expressed in monoclonal autoantibodies from autoimmune mice revealed that similar, and in some instances even identical, gene segments are expressed in autoantibodies and in antibodies to exogenous antigens, and that anti-self and anti-non-self responses are encoded by the same, or at least an overlapping germline gene repertoire. A large variety of Ig variable (V), diversity (D), and joining (J) gene segments can encode autoantibodies with different specificities, and both germline genes and somatically-mutated genes can be expressed in such antibodies.