Higher proliferative response in B-chronic lymphocytic leukemia (B-CLL) as compared to B-monoclonal lymphocytosis of undetermined significance (B-MLUS) after stimulation with Staphylococcus aureus and anti-CD40 monoclonal antibodies

Abstract B-CLL is a malignant monoclonal B-cell disorder and B-MLUS is the benign counterpart. The proliferative response and the capacity to secrete IgM was measured in B-CLL and B-MLUS, respectively, and compared to normal B-cells. SAC and a mAb against CD40 were used as stimulatory agents. No cell population responded to anti-CD40 mAb alone. SAC only induced a high DNA synthesis rate in normal B-cells as well as in B-CLL cells, although the magnitude was three-fold lower and delayed for about 48 h in B-CLL. B-MLUS cells did not proliferate in response to SAC. The combination of anti-CD40 and SAC enhanced the proliferative capacity of normal B-cells and produced a more rapid response in B-CLL. B-MLUS cells were not activated. Normal B-cells and B-MLUS did not secrete IgM after SAC stimulation, while B-CLL cells had a continuous increase in the IgM production during a 6-day culture period. The higher proliferative capacity of B-CLL cells compared with B-MLUS cells may be explained by an increased expression of activation molecules e.g. receptors for various cytokines and growth factors. Moreover, the inertness and inability of B-MLUS cells in comparison to normal B- and B-CLL cells to respond to powerful activation signals might indicate an intrinsic defect of B-MLUS cells in the signal transduction leading to a block of mitosis and a benign course of the disease.