title: [Autoantibodies, tolerance and autoimmunity].
abstract: In 1900, the group from Metchnikoff suggested the concept of autoimmunization by demonstrating the presence of autoantibodies in normal conditions; which was opposed to the concept of horror autotoxicus raised by Ehrlich. Landsteiner's description of the transfusion compatibility rules and 50 year-later work from Burnett's and Medawar's groups lead to the clonal deletion theory as a general explanation of tolerance and autoimmunity. However, more recent work succeeded demonstrating that autoreactive B cells constitute a substantial part of the B-cell repertoire and that this autoreactive repertoire secretes the so-called natural autoantibodies (NAA) characterized by their broad reactivity mainly directed against very well conserved public epitopes. They fulfill the definition of an autoantibody since they are self-reactive, but they are not self-specific. As yet, NAA directed against determinants of polymorphism have not been reported. The presence of this repertoire in normal conditions challenges the clonal deletion theory as a unique explanation for self-tolerance. However, if we take into account that this autoreactive B-cell repertoire is not self-specific, this contradiction may not be a real one opposition. Indeed, the Lansteiner's rule that a subject belonging to group A will never produce anti-A antibodies and will always produce natural antibodies against the B-cell group, could never be challenged. Clonal deletion is probably accounting for this phenomenum. However, the serum of healthy adult individuals frequently exhibits low titers of anti-I antibodies, which is a precursor molecule of AB0 antigen system. The mechanism accounting for deletion of B cells directed against critical determinants like antigens A and B in the red blood cell system and allowing the production of autoantibodies against I remain elusive.
authors.affiliation: Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur, 28, rue du Dr Roux, 75724 Paris, France.
authors.forename: Pablo
authors.initials: P
authors.lastname: Oppezzo
authors.forename: Guillaume
authors.initials: G
authors.lastname: Dighiero
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology; D001323:Autoantibodies; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D002240:Carbohydrate Sequence; D006801:Humans; D007048:I Blood-Group System / Q000737:chemistry / Q000276:immunology; D007108:Immune Tolerance; D008969:Molecular Sequence Data
chemical_list: D000017:ABO Blood-Group System; D001323:Autoantibodies; D001324:Autoantigens; D007048:I Blood-Group System