Interleukin-15 enhances HIV-1-driven polyclonal B-cell response in vitro

Interleukin-15 (IL-15) is a recently described cytokine, produced by monocytes/macrophages, with biological activities similar to IL-2. Since IL-15 was shown to stimulate human B-cell proliferation and immunoglobulin secretion, we investigated its effect on human B-cells stimulated with heat-inactivated human immunodeficiency virus type 1 (iHIV-1) in vitro. We observed a dose-dependent elevation of [H-3]-thymidine incorporation and immunoglobulin production by B-cells incubated in the presence of iHIV-1. Moreover, IL-15 stimulated HIV-1-driven B-cell proliferation similarly to IL-2. As to immunoglobulin secretion, IL-15 was able to potentiate the stimulatory effect of IL-10. The highest amounts of iHIV caused a decrease in B-cell proliferation and immunoglobulin secretion to baseline levels, even in the presence of cytokines. These findings indicate that during the late stages of AIDS, when monocytes/macrophages become the major site of viral production, IL-15, in concert with other monocyte-derived cytokines, may promote polyclonal B-cell activation and hypergammaglobulinaemia, which are frequently associated with HIV infection.