BCR and B-cell chronic lymphocytic leukemia: Unlike other B cell malignancies, BCRs on CLL cells are unique in that they can ligate each other via Ig heavy-chain CDR3 of one BCR with the framework region 2 of another BCR, regardless of their IGHV mutation statuses, thereby providing antigen-independent, cell-autonomous signaling [2,52] (Figure 7B).