There is evidence indicating that autoreactive B cells constitute a substantial part of the B-cell repertoire. This autoreactive repertoire secretes the so-called natural autoantibodies characterized by their broad reactivity mainly directed against well conserved public epitopes. Their germinal origin is suggested by their early appearance during ontogeny, their expression of cross-reactive idiotopes and structural studies of their sequence. As for the physiological role of the repertoire, they may play a major role as a first barrier of defense. It is presently unknown whether, or not, these polyreactive B cells could constitute a pre-immune template which through an antigen-driven process may be involved in the production of immune high affinity antibodies. Studies carried out in monoclonal gammopathies, chronic lymphocytic leukemia and follicular lymphomas, demonstrated that this autoreactive B-cell repertoire frequently undergoes malignant transformation, although there is controversy concerning the reasons for this. It has been postulated that the continuous challenge of this autoreactive repertoire by self-antigens could create propitious conditions for malignant transformation to occur. However, this hypothesis needs to be substantiated.

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