Dw. Metzger et al., INTERLEUKIN-12 ACTS AS AN ADJUVANT FOR HUMORAL IMMUNITY THROUGH INTERFERON-GAMMA-DEPENDENT AND INTERFERON-GAMMA-INDEPENDENT MECHANISMS, European Journal of Immunology, 27(8), 1997, pp. 1958-1965
Interleukin-12 (IL-12) is a pivotal cytokine that has dramatic effects
on cell-mediated immunity. It is now becoming increasingly recognized
that IL-12 also strongly controls humoral immunity. We have investiga
ted the mechanism by which IL-12 induces alterations in antibody isoty
pe expression by determining the influence of IL-12 on in vitro immuno
globulin (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 gamma 2a g
erm-line transcripts, consistent with initiation of switch recombinati
on to IgG2a. In addition, exposure of limiting dilution cultures to IL
-12 increased IgG2a(+) cell precursor frequency. All of the above resu
lts were dependent on interferon-gamma (IFN-gamma). However, in the ab
sence of IFN-gamma, IL-12 still had significant effects on Ig secretio
n. Specifically, IL-12 enhanced IgG1 and IgG2b anti-DNP antibody level
s in mice containing specific disruptions in the IFN-gamma gene. Our r
esults suggest that IL-12 induces T helper type 1 and natural killer c
ells to secrete large amounts of IFN-gamma which then causes B cells t
o switch to IgG2a and IgG3 production, In addition, IL-12 has direct o
r indirect effects on B cells that are independent of IFN-gamma. The I
FN-gamma-independent effects may include enhancement of Ig expression
by post-switched cells.