Ehrlich's and Metchnikoff's postulates on tolerance and autoimmunity may not be incompatible, after all

In 1900, the group from Metchnikoff suggested the concept of autoimmunizati on by demonstrating the presence of autoantibodies in normal conditions; wh ich was opposed to the concept of horror autotoxicus raised by Ehrlich. Lan dsteiner's description of the transfusion compatibility rules and 50 year-l ater work from Burnett's and Medawar's groups lead to the clonal deletion t heory 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 reper toire secretes the so-called natural autoantbodies (NAA) characterized by t heir broad reactivity mainly directed against very well conserved public ep itopes. They fulfill the definition of an autoantibody since they are self- reactive, but they are not self-specific. As yet, NAA directed against dete rminants of polymorphism have not been reported The presence of this repert oire? in normal conditions challenges the clonal deletion theory as a uniqu e explanation for self-tolerance. However, if we take into account that thi s autoreactive B-cell repertoire is not self-specific, this contradiction m ay not be a real one opposition. Indeed the Lansteiner's rule that a subjec t belonging to group A will never produce anti-iii antibodies and will alwa ys produce natural antibodies against the B-cell group, could never be chal lenged. 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 ABO antigen system. The mechanism accounting for deletion of B cells directed against critical dete rminants like antigens A and B in the red blood cell system and allowing th e production of autoantibodies against I remains elusive.