Brain-derived neurotrophic factor (BDNF) has potent effects on neuronal survival and plasticity during development and after injury. In the nervous system, neurons are considered the major cellular source of BDNF. We demonstrate here that in addition, activated human T cells, B cells, and monocytes secrete bioactive BDNF in vitro. Notably, in T helper (Th)1- and Th2-type CD4+ T cell lines specific for myelin autoantigens such as myelin basic protein or myelin oligodendrocyte glycoprotein, BDNF production is increased upon antigen stimulation. The BDNF secreted by immune cells is bioactive, as it supports neuronal survival in vitro. Using anti-BDNF monoclonal antibody and polyclonal antiserum, BDNF immunoreactivity is demonstrable in inflammatory infiltrates in the brain of patients with acute disseminated encephalitis and multiple sclerosis. The results raise the possibility that in the nervous system, inflammatory infiltrates have a neuroprotective effect, which may limit the success of nonselective immunotherapies.

Although the aetiology of systemic lupus erythematosus (SLE) is unclear, dysregulated B cell responses have been implicated. Here we show that an unusual CD11chiT-bet+ B cell subset, with a unique expression profile including chemokine receptors consistent with migration to target tissues, is expanded in SLE patients, present in nephrotic kidney, enriched for autoreactive specificities and correlates with defined clinical manifestations. IL-21 can potently induce CD11chiT-bet+ B cells and promote the differentiation of these cells into Ig-secreting autoreactive plasma cells. While murine studies have identified a role for T-bet-expressing B cells in autoimmunity, this study describes and exemplifies the importance of CD11chiT-bet+ B cells in human SLE.

The number of neurotrophic factors found in the central nervous system is rapidly growing, but their functions in vivo are largely unknown. In the peripheral nervous system they promote the survival of developing and lesioned neurons and enhance nerve fibre growth and regeneration. Here we study the effects of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) on the largest tract system leading from the brain to the spinal cord, the corticospinal tract (CST). The developing CST grows down the spinal cord during the first postnatal days and innervates its targets after a waiting period by collateral sprouting. We find that NT-3 injected locally specifically enhances this sprouting, whereas BDNF has no effect. In adult rats, injection of NT-3 (but not BDNF) into the lesioned spinal cord increases the regenerative sprouting of the transected CST. The distance of growth of the sprouts is very restricted, but application of an antibody that neutralizes myelin-associated neurite growth inhibitory proteins results in long-distance regeneration of CST fibres.