The role of BAFF in central nervous system inflammation

B cell activating factor (BAFF) is critical for B cell survival, a function that is mediated by BAFF receptor, (BAFF-R). Systemic BAFF overexpression is sufficient to cause lupus-like autoimmune disease. Using a genetic approach, and generating transgenic mice which constitutively express BAFF under the control of the glial fibrillary acidic protein (GFAP) promoter in astrocytes, BAFF was shown to regulate both innate and adaptive immune responses in central nervous system (CNS) inflammation. BAFF-R deficiency resulted in increased severity of experimental autoimmune encephalomyelitis (EAE) which was associated with elevated BAFF expression. Inflammatory foci comprised increased numbers of activated macrophages expressing BAFF and correlated with increased BAFF secretion in the periphery. Constitutive CNS BAFF expression in astrocytes altered the course of EAE to a relapsing remitting form of EAE superimposed on a chronic or progressive form. Thus, BAFF-R may be important in regulating EAE possibly by influencing macrophage function through a mechanism which may involve modulation of BAFF expression, whereas constitutive CNS BAFF expression in astrocytes may be important in the development of relapses and remissions and progression of EAE, possibly through increased autoantibody or T cell-mediated CNS inflammation which may result in epitope spreading; as well as through its effects on the regulation of B and T cells, and macrophage activation in the CNS.