BCR and B-cell chronic lymphocytic leukemia: This indicates that antigenic signaling continues throughout the disease course and that the BCR is engaged primarily in the LN, rather than in the PB.3 Consistent with chronic antigen contact in vivo is the observation of a reversible down-modulation of surface IgM expression on CLL cells and the resemblance of these cells to anergic B-cells.22, 23