The historical key-concept of humoral immunity is based on three major properties of antibodies (Abs): nonself-specificity, monospecificity and immune memory. In 1900, a group from Metchnikoff suggested the concept of autoimmunization by demonstrating the presence of autoantibodies in normal con ditions [1, 2]; which was opposed to the concept of horror autotoxicus raised by Ehrlich and Morgenroth [3, 4], At nearly the same time, Landsteiner

[5] described the rules governing blood compatibility. He showed that a subject will never be able to produce auto-Abs against the major blood group antigens. These results provided strong support for Ehrlich and Morgenroth's idea. Although, Metalnikoff [1] clearly demonstrated that animals were able to produce autoantibodies against spermatozoids, their significance was soon confined to the convenient explanation of a pathological process. The influence of Ehrlich ideas was so strong that these experiments were forgotten, and when Donath and Landsteiner

[6] described an autoantibody for the first time— the biphasic hemagglutinin responsible for paroxismal cold hemoglobinuria—they failed to call it an autoantibody.

In 1949, Burnet and Fenner [7] proposed the clonal deletion theory, which was strongly influenced by the experiments conducted by Owen [8] with dizygotic calfs sharing a single placenta. The red blood cells from these two calfs were mixed but, despite the fact that they expressed different blood groups, they were displaying double populations of red blood cells at birth, and each was unable to produce alloantibodies against the blood group from the other. The interpretation of these experiments led Burnet and Fenner [7] to elaborate on the clonal deletion theory. This was an excellent theory that explained tolerance and autoimmunity in a simple way. Autoimmunity, according to this theory, would only arise as a consequence of somatic mutation, which is an unusual phenomenon.

During recent years, however, evidence has emerged indicating that the autoreactive repertoire is an important component of the normal B-cell reper toire which is frequently involved in malignant transformation.

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