Polyclonal hypergammaglobulinaemia in a case of B-cell chronic lymphocytic leukaemia: the result of IL-2 production by the proliferating monoclonal B cells?

SEQ DATA who developed polyclonal hypergammaglobulinaemia: 38.3 milligrams polyclonal IgG, 0.97 milligram IgA and 0.33 milligram IgM. Immunophenotyping showed a monoclonal lymphocytic population CD19+ CD5+ CD40+ CD23+, low sIg+ (95%), kappa type in the great majority (96%). RT-PCR of immunoglobulin genes gave evidence of monoclonal rearrangement of the IgM type. Our tests showed that IL-2 was produced when leukaemic B cells were stimulated with phorbol myristate acetate, ionomycin and lipopolysaccharide. In addition, transfections with the full IL-2 promoter or elements thereof revealed that IL-2 expression is inducible and mediated through the NF-kB-promoter element. Finally, the amount of IL-2 secreted by these cells is about 39 ng/ml/10(6) cells, which is remarkably high for non-T cells. These results suggest that the large amounts of polyclonal IgG seen in this case of B-CLL are secreted by normal B cells which are in turn stimulated by IL-2 produced by proliferating monoclonal (leukaemic) B cells. Under cyclosporin A treatment, immunoglobulin secretion and B cell count remained low.