NERVE GROWTH-FACTOR IS AN AUTOCRINE SURVIVAL FACTOR FOR MEMORY B-LYMPHOCYTES

Production of nerve growth factor (NGF) was assessed in cultures of hu man T and B lymphocytes and macrophages. NGF was constitutively produc ed by B cells only, which also expressed surface p140(trk-A) and p75(N GFR) molecules and hence efficiently bound and internalized the cytoki ne. Neutralization of endogenous NGF caused disappearance of Bcl-2 pro tein and apoptotic death of resting lymphocytes bearing surface IgG or IgA, a population comprising memory cells, while surface IgM/IgD ''vi rgin'' B lymphocytes were not affected. In vivo administration of neut ralizing anti-NGF antibodies caused strong reduction in the titer of s pecific lgG in mice immunized with tetanus toroid, nitrophenol, or ars onate and reduced numbers of surface IgG or IgA B lymphocytes. Thus, N GF is an autocrine survival factor for memory B lymphocytes.