The Pathologic Significance of the Immunoglobulins Expressed by Chronic Lymphocytic Leukemia B-cells in the Development of Autoimmune Hemolytic Anemia

Abstract

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 51 p1 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 51 p1 V_H gene may be at a higher risk to develop autoimmune hemolytic anemia.

Key Words:

• Autoimmune hemolytic anemia
• chronic lymphocytic leukemia
• CD5 B-cells
• rheumatoid factor
• V_H gene