There is consistent evidence indicating that autoreactive B cells constitute a substantial part of the B-cell repertoire. This autoreactive repertoire secretes natural autoantibodies, which are frequently germline encoded, display a widespread reactivity and may play an important physiological 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 may be involved through an antigen-driven process in the production of immune high affinity antibodies.

This autoreactive B-cell repertoire frequently undergoes malignant transformation, although there is controversy concerning the reasons accounting 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, it can be alternatively hypothesized that overexpression of certain genes reflect what happens during ontogeny, since V genes expression is a developmentally regulated phenomenon and not all V genes are expressed during fetal life [73-74]. Some of the genes that are recurrently expressed by these malignancies are also overexpressed in fetal repertoires and even in the adult normal B-cell repertoire. We do not know whether it is the challenge by self-antigens or alternatively whether this overexpression simply reflects what happens with the fetal repertoire which could have selective advantages for malignization.

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