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

Interleukin-15 (IL-15) is a recently described cytokine, produced by monocy tes/macrophages, with biological activities similar to IL-2. Since IL-15 wa s shown to stimulate human B-cell proliferation and immunoglobulin secretio n, we investigated its effect on human B-cells stimulated with heat-inactiv ated human immunodeficiency virus type 1 (iHIV-1) in vitro. We observed a d ose-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 immu noglobulin secretion, IL-15 was able to potentiate the stimulatory effect o f IL-10. The highest amounts of iHIV caused a decrease in B-cell proliferat ion and immunoglobulin secretion to baseline levels, even in the presence o f cytokines. These findings indicate that during the late stages of AIDS, w hen 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 associat ed with HIV infection.