Autoantibodies, tolerance and autoimmunity

• Published in: Pathologie biologie (Paris) 2003-07, Vol.51 (5), p.297
• Main Authors: Oppezzo, Pablo, Dighiero, Guillaume
• Format: Article
• Language: fre
• Subjects: ABO Blood-Group System - immunology; Autoantibodies; Autoantigens - chemistry; Autoantigens - immunology; Autoimmunity; B-Lymphocytes - immunology; Carbohydrate Sequence; Humans; I Blood-Group System - chemistry; I Blood-Group System - immunology; Immune Tolerance; Molecular Sequence Data
• ISSN: 0369-8114
• DOI: 10.1016/S0369-8114(02)00318-8

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.