Nerve growth-factor and anti-CD40 provide opposite signals for the production of IgE in interleukin-4-treated lymphocytes

Nerve growth factor (NGF) is a well-known neurotrophic factor acting on both the peripheral and the central nervous systems. In addition, it has been shown to play a role in the function of the immune system through specific receptors. Both high-affinity and low-affinity NGF receptors (NGFR) are expressed on human B lymphocytes. The low-affinity NGFR has been shown to have structural homology with another specific B cell surface molecule, CD40, which plays an important role in IgE production. In view of the structural similarities of the p75 NGFR and CD40 we examined whether NGF may also be involved in the regulation of IgE production. We found that NGF and anti-CD40 exerted opposite effects on the induction of IgE by IL-4 in peripheral blood mononuclear cells. NGF inhibited the induction of IgE by IL-4 and this inhibition was not mediated through blocking of the induction of CD23 nor through inhibition of IL-IR expression. The inhibition of IL-4-dependent IgE production was observed on surface (s)IgE(+) and sIgE-/sIgM(+) B lymphocytes. Anti-CD40 on the other hand. exerted an enhancing effect on IgE production and its addition to IL-4 provided a signal that was resistant to the inhibitory effect of NGF. Antagonistic effects of NGF and IL-4 were also observed for other Ig isotypes since IL-4 prevented the increase in IgA and IgM production induced by NGF. These data indicate that although NGFR and CD40 belong to the same receptor superfamily and exert similar proliferative effects on B lymphocytes, they interact differently with IL-4 in the regulation of IgE production.