NERVE GROWTH-FACTOR SPECIFICALLY INDUCES HUMAN IGG4 PRODUCTION

The effect of nerve growth factor (NGF) on human IgG4 production was studied. NGF specifically enhanced IgG4 production in cultures of human tonsillar mononuclear cells without affecting production of other isotypes or other IgG subclasses. Optimal enhancement of IgG4 production by NGF required the presence of T cells. However, NGF induced significant IgG4 production by small resting B cells in the absence of T cells, and this production was enhanced by stimulation with Staphylococcus aureus Cowan strain I (SAC). In contrast to small B cells, large activated B cells produced IgG4 spontaneously; this production was enhanced by NGF. NGF also enhanced IgM and IgA production by large B cells, while production of IgG1, IgG2, IgG3 and IgE was not affected. The enhancement of IgG4 production was blocked by anti-NGF serum but not by control serum. NGF, T cells and SAC, separately or together, failed to induce IgG4 production by surface (sIgG4+)-depleted B cells. In contrast to NGF, other recombinant human cytokines including interleukin (IL) 1-beta, IL 2, IL 4, IL 5, IL 6, granulocyte-macrophage colony-stimulating factor, interferon-alpha and gamma-failed to induce IgG4 production. These results suggest that NGF directly and preferentially stimulates activated sIgG4+ B cells to produce IgG4.