Identification in CLL of circulating intraclonal subgroups with varying B-cell receptor expression and function

摘要: Chronic lymphocytic leukemia (CLL) is a tumor of circulating B cells, variably stimulated and anergized following exposure to antigen in lymphoid tissues. Down-modulation surface IgM (sIgM) occurs, but expression signal capacity can recover vitro apparently vivo during recirculation. We have now dissected individual clones CLL cases according sIgM level by differential binding bead-bound anti-IgM. Four clear subgroups (SG1-4) with increasing were identified 37/37 cases. Engagement induced phosphorylation PLCγ2 ERK1/2 at levels ranging from very low SG1 high SG4. Phosphorylation was suppressed the BTK inhibitor ibrutinib. Expression CXCR4 also increased SG4, markers previous activation proliferation dominant SG1. Incubation whole populations led striking increases as well recovery sIgM. Clonal analysis reveals dynamic SGs presumed stimulation SG4 represents fully recovered, potentially dangerous population equipped migrate tissue receive proliferative stimulus. likely postmitotic unresponsive "resting" population. The effect ibrutinib on small may be critical factor therapeutic success.