BAFF Controls Neural Cell Survival through BAFF Receptor

Abstract

Various neuroprotective factors have been shown to help prevention of neuronal cell death, which is responsible for the progression of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). However, most of these therapeutic potentials have been tested by administration of recombinant proteins, transgenic expression or virus vector-mediated gene transfer. Therefore, it remains to be clarified whether any endogenous factors has advantage for neuroprotection in a pathological nervous system. Here we show the role of BAFF-R signaling pathway in the control of neural cell survival. Both B cell–activating factor (BAFF) and its receptor (BAFF-R) are expressed in mouse neurons and BAFF-R deficiency reduces the survival of primary cultured neurons. Although many studies have so far addressed the functional role of BAFF-R on the differentiation of B cells, impaired BAFF-R signaling resulted in accelerated disease progression in an animal model of inherited ALS. We further demonstrate that BAFF-R deficient bone marrow cells or genetic depletion of B cells does not affect the disease progression, indicating that BAFF-mediated signals on neurons, not on B cells, support neural cell survival. These findings suggest opportunities to improve therapeutic outcome for patients with neurodegenerative diseases by synthesized BAFF treatment.

The Immunoregulator Soluble TACI Is Released by ADAM10 and Reflects B Cell Activation in Autoimmunity

“…The fact that atacicept increased disease activity in MS patients(9), whereas in SLE it showed beneficial clinical effects (10), remains incompletely understood. Expression of BAFF-R on neurons was observed(46). So one could speculate that atacicept could limit neuronal survival by decreasing BAFF-levels.…”

Fingolimod induces neuroprotective factors in human astrocytes

“…Therefore, BAFF is thought to be a relevant part of the B-cell fostering environment and to perpetuate the immune response observed in the CNS of patients with MS [ 45 ]. In addition, BAFF was reported to bind to rodent neurons via BAFF-R [ 46 ] and NOGO-R [ 47 ]. Functional consequences in humans deserve further elaboration.…”

Meningeal Infiltration of the Spinal Cord by Non-Classically Activated B Cells is Associated with Chronic Disease Course in a Spontaneous B Cell-Dependent Model of CNS Autoimmune Disease

“…By contrast, TACI-Fc does target plasma cells in addition to mature B cells. Further, as both T cells and neurons express receptors for BAFF ( 20 , 21 ), the effects of this drug likely extend well beyond B cell depletion. Therefore, while antibodies may contribute to pathology ( 1 ), the primary B cell contribution to MS is through some other mechanism(s), perhaps via APC function or cytokine modulation of the autoimmune response.…”