[Apparently opposite postulates of Ehrlich (Horror autotoxicus) and Metchnikoff (physiological autoimmunization) are not irreconcilable].
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 phenomenon. 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 remains elusive.
Dighiero
G
G
Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur, Paris. dighiero@pasteur.fr
D000017:ABO Blood-Group System / Q000235:genetics / Q000276:immunology; D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D005075:Biological Evolution; D001782:Blood Donors; D017637:Clonal Deletion; D006801:Humans; D007108:Immune Tolerance; D007136:Immunoglobulins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009101:Multiple Myeloma / Q000276:immunology; D009154:Mutation; D008258:Waldenstrom Macroglobulinemia / Q000276:immunology
D000017:ABO Blood-Group System; D001323:Autoantibodies; D007136:Immunoglobulins