The pathologic significance of the immunoglobulins expressed by chronic lymphocytic leukemia B-cells in the development of autoimmune hemolytic anemia

The increased number of CD5(+) B-cells in some human autoimmune diseases, the frequent commitment of CD5(+) B-cells to the production of natural autoantibodies, and the apparent involvement of these cells in the pathogenesis of the autoimmune hemolytic anemia (AIHA) in certain mouse models suggests a causal relationship between the CD5(+) chronic lymphocytic leukemia (CLL) B-cell and the AIHA which frequently develops in this malignant disorder. In support of this conclusion is our recent finding that the V-H, region gene repertoire of the leukemic B-cells from CLL patients with AIHA is rather biased and characterised by the over-representation of the 51p1 V-H gene. On the other hand, it appears relatively certain that the pathogenic anti-erythrocyte antibodies in CLL patients with AIHA are produced by remnant normal B-cells, and that the antibodies expressed by the leukemic CD5(+) B-cells do not directly bind red blood cells (RBC). Of interest, the antibodies produced by the leukemic B-cells from CLL patients with AIHA might have in common rheumatoid factor (RF) activity. These data indicate that the antibodies produced by the leukemic B-cells from CLL patients with AIHA are not directly involved in red blood cell destruction, but may be involved in the induction or amplification of a polyclonal anti-RBC response. Finally, we discuss the possible clinical implications of our finding that CLL patients with leukemic cells expressing the 51p1 V-H gene may be at a higher risk to develop autoimmune hemolytic anemia.