Nerve growth factor induces growth and differentiation of human B lymphocytes

Nerve growth factor (NGF) is known to affect peripheral sympathetic and sensory neurons as well as defined populations of neurons in the central nervous system. This paper presents evidence that NGF is also active in modulation of B-cell-mediated immune responses. NGF receptors were immunoprecipitated from highly purified human B-cell populations, and to a lesser extent, from T-cell populations, by using a monoclonal antibody recognizing NGF receptors present on neural cells. NGF receptors were also detected in significant amounts in human spleen and lymph node tissue. In addition, NGF induced a dose-dependent increase in B-cell DNA synthesis as determined by incorporation of [3H]thymidine. This B-cell growth-promoting activity was inhibited by a neutralizing anti-NGF monoclonal antibody. Immunoglobulin secretion, principally affecting IgM synthesis, was also modulated by NGF. The concentrations that affected B-cell proliferation are consistent with the presence of functional high-affinity NGF receptors. The results suggest that NGF, in addition to its neurotrophic function, also acts as an immunoregulatory cytokine.