Nerve growth factor (NGF) is a neurotrophic factor acting on both the peripheral and central nervous systems. In addition, it has been shown to modulate B lymphocyte function through receptors consisting of both p75 and TrkA proteins. The low-affinity NGFR, p75, shares structural homology with the B cell antigen, CD40, tumor necrosis factor (TNF) receptor and Fas antigen (APO-1), which play a role in cell apoptosis. We studied the effect of NGF on anti-IgM-induced apoptosis in human B lymphocytes and the role of protein kinase C (PKC) in this effect. Incubation of Ramos cells with anti-IgM (10 μg/ml) induced apoptosis which was observed after 6 h and reached plateau levels after 24 h. Addition of NGF to anti-IgM-treated cells rescued cells from apoptosis. The NGF effect was blocked by anti-NGF antibody and by K252a, a specific inhibitor for the tyrosine kinase activity of TrkA. NGF induced translocation of PKCδ and PKCα from the cytosol to the plasma membrane and translocation of PKCζ to the nucleus. To examine the role of PKC in the inhibitory effect of NGF on anti-IgM-induced apoptosis, we used inhibitors of PKCα and PKCδ and found that these treatments did not alter the NGF effect. In contrast, treatment of the cells with oligonucleotide antisense directed against the 5′ coding sequence of PKCζ reduced the expression of PKCζ in the cells and abolished the protective effect of NGF on anti-IgM-induced apoptosis. The translocation of PKCζ and the protective effect of NGF were inhibited by the phosphatidylinositol 3 (PI3)-kinase inhibitors wortmannin and LY294002. The results of this study indicate that NGF is involved in B cell survival and that this effect is mediated by PI3-kinase-dependent activation of PKCζ.
|Number of pages||8|
|Journal||European Journal of Immunology|
|State||Published - 2002|
- B lymphocyte
- Nerve growth factor