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

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Interleukin-15 (IL-15) is a cytokine produced by monocytes/macrophages with IL-2-like activities.
• IL-15 is known to stimulate B-cell proliferation and immunoglobulin secretion.
• HIV infection is associated with B-cell abnormalities and hypergammaglobulinaemia.

Purpose of the Study:

• To investigate the effect of IL-15 on human B-cells stimulated with heat-inactivated HIV-1 (iHIV-1) in vitro.
• To compare the effects of IL-15 and IL-2 on HIV-1-driven B-cell responses.
• To explore the role of IL-15 in potentiating immunoglobulin secretion.

Main Methods:

• In vitro culture of human B-cells with iHIV-1 and varying concentrations of IL-15.
• Measurement of [3H]-thymidine incorporation to assess B-cell proliferation.
• Quantification of immunoglobulin production.
• Assessment of IL-15's effect in combination with IL-10.

Main Results:

• IL-15 dose-dependently increased [3H]-thymidine incorporation and immunoglobulin production in B-cells exposed to iHIV-1.
• IL-15 mimicked IL-2 in stimulating HIV-1-driven B-cell proliferation.
• IL-15 potentiated the immunoglobulin secretion induced by IL-10.
• High iHIV-1 concentrations reduced B-cell proliferation and immunoglobulin secretion, overriding cytokine effects.

Conclusions:

• IL-15 promotes polyclonal B-cell activation and immunoglobulin production in the context of HIV-1 stimulation.
• IL-15, along with other monocyte-derived cytokines, may contribute to hypergammaglobulinaemia in late-stage AIDS.
• These findings highlight IL-15's potential role in the immune dysregulation associated with HIV infection.