Complex causes of these low immunoglobulin levels (Igs) include defective production of polyclonal Igs due to abnormal function of non-clonal CD5− B cells; impaired IgG and IgA class-switch through abnormal CD40–CD40L interaction and down-modulation of CD40L (24, 25); impaired help and excessive suppression by T-cells (26, 27); sequestration of T-cell help by CLL cells in pseudofolicles (7), inhibition of CD95+ plasma cells in the bone marrow via interaction with CD95L on CLL B-cells (28), and iatrogenic myelosuppressive chemotherapy (9, 21). This evidence concerns the gene CD40 and B-cell chronic lymphocytic leukemia.