title: The role of somatic hypermutation in the generation of pathogenic antibodies in SLE.
abstract: The formation of antibodies against double-stranded (ds)DNA is considered to be the serologic hallmark of systemic lupus erythematosus (SLE) and anti-dsDNA antibodies play an important role in the pathogenesis of the disease. Anti-dsDNA antibodies from lupus mice and SLE patients arise by somatic mutation. Importantly, autoantibodies in which somatic mutations have been reverted to germ-line V regions did not show any measurable autoreactivity, suggesting that anti-dsDNA autoantibodies develop from non-autoreactive B-cells by somatic hypermutation, presumably during the germinal center reaction. As the random nature of somatic hypermutation will inevitably create autoreactive B cells, self-tolerance checkpoints at the postmutational stage of B cell differentiation have to exist that normally prevent the induction of pathogenic anti-dsDNA specificities. This review summarizes the proposed mechanisms for the generation of anti-dsDNA in murine lupus and in SLE patients.
authors.affiliation: Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Schroeder
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Winkler
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics / Q000276:immunology; D000917:Antibody Formation / Q000235:genetics*; D001323:Autoantibodies / Q000096:biosynthesis*; D004247:DNA / Q000276:immunology; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D007135:Immunoglobulin Variable Region; D004247:DNA