B-chronic lymphocytic leukemia: a malignancy of anti-self B cells

B -CHRONIC lymphocytic leukemia (B-CLL) is the most common leukemia in the western world.It is characterized by the relentless accumulation of mature CD5+ B cells' (B1 B cells, according to the new nomenclature') and by a remarkably high frequency of autoimmune phen~mena,~ For these reasons, B-CLL has been widely used as a model for the study of lymphoproliferative disorders and has given a great impulse to the study of the role of CD5' B cells in autoimmunity.From these studies CD5' B-CLL cells have emerged as a crossroad between malignant and autoreactive B cells.Enough information is now available to put the unique biological and clinical features of B-CLL into a unifying perspective.The essence of the problem to be reviewed is threefold.First, CD5+ B-CLL B cells express low to undetectable amounts of surface immunoglobulins SI^).^Second, B-CLL B cells accumulate in the GO phase of the cell Third, the pathogenic autoantibodies (Abs), detectable in up to 30% of the patients, are usually polyclonal and target-re-stri~ted.~.~,'They are directed against hematopoietic antigens expressed on the surface of red blood cells and, more rarely, of platelets and may lead to severe autoimmune hemolytic anemia and/or thromb~cytopenia.~"~'These features led us to ask which is the actual normal counterpart of B-CLL B lymphocyte and how the molecular events that result in the malignant phenotype relate to the development of autoimmune manifestations.