SUMMARY REMARKS ON THE DEVELOPMENT, GROWTH, AND EVOLUTION OF B-CLL
On the basis of the foregoing information, we propose a model for the development of B-CLL. B-CLL cells are able to avoid apoptosis and even to proliferate by receiving growth and stimulatory signals from the environment delivered through their BCR or other receptors; these signals likely involve autologous and foreign antigens, cytokines, and chemokines, as well as yet-to-be-defined ligand on accessory and stromal cells. The cell’s BCR mediates major growth effects in cases for which the receptor is polyreactive, binding autoantigens and foreign antigens, while maintaining its capacity to transmit stimulatory signals to the cell nucleus. Both self-reactivity and intact BCR signal-transducing capacity are more frequently found in U-CLL;hence, the more active clonal expansion and clinical aggressiveness of patients with such clones.