Interleukin‐12 acts as an adjuvant for humoral immunity through interferon‐γ‐dependent and ‐independent mechanisms

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Abstract
Interleukin-12 (IL-12) is a pivotal cytokine that has dramatic effects on cellmediated immunity. It is now becoming increasingly recognized that IL-12 also strongly controls humoral immunity. We have investigated the mechanism by which IL-12 induces alterations in antibody isotype expression by determining the influence of IL-12 on in vitro immunoglobulin (Ig) production in polyclonally activated murine spleen cell cultures. Cells exposed to IL-12 plus lipopolysaccharide or anti-CD40 monoclonal antibody showed dramatically elevated IgG2a and suppressed IgG1 production compared to cells cultured in the absence of IL-12. IL-12 treatment of spleen cell cultures induced expression of γ2a germ-line transcripts, consistent with initiation of switch recombination to IgG2a. In addition, exposure of limiting dilution cultures to IL-12 increased IgG2a+ cell precursor frequency. All of the above results were dependent on interferon-γ (IFN-γ). However, in the absence of IFN-γ, IL-12 still had significant effects on Ig secretion. Specifically, IL-12 enhanced IgG1 and IgG2b anti-DNP antibody levels in mice containing specific disruptions in the IFN-γ gene. Our results suggest that IL-12 induces T helper type 1 and natural killer cells to secrete large amounts of IFN-γ which then causes B cells to switch to IgG2a and IgG3 production. In addition, IL-12 has direct or indirect effects on B cells that are independent of IFN-γ. The IFN-γ-independent effects may include enhancement of Ig expression by post-switched cells.

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