Finally and third, why does a single mutation, S707Y, of PLCG2 cause, on the one hand, autoinflammation when occurring in the germline, with no evidence yet for increased development of B cell malignancies in the affected APLAID patients, and, on the other hand, progression of B cell malignancies to drug-resistance when occurring somatically in CLL cells? The gene discussed is PLCG2; the disease is B-cell chronic lymphocytic leukemia.