B Cells Producing Pathogenic Autoantibodies

Abstract Immunoglobulins are generated in B cell precursors through random recombination of V, (D), and J gene segments. Although this process creates an enormous repertoire of antibodies that are able to recognize and eradicate virtually all microbes, it also inevitably produces antibodies that react with antigens of the organism's own tissues. Tolerance mechanisms prevent most developing B cells with autoreactivity from reaching a mature immunocompetent stage. A second wave of generation of autoreactive antibodies occurs in antigen-stimulated GCs through somatic hypermutation, and, again, censoring mechanisms are required. Autoantibodies are found in healthy individuals. Some germline-encoded autoantibodies even have protective properties. Autoantibodies may, however, lead to full-blown autoimmune disorders. This chapter summarizes the origin of autoantibodies and describes their pathogenicity in the context of some selected autoimmune diseases.