Maha Bakhuraysah
Taif University, Saudi Arabia
Title: A novel immune role for NgR on b-cell populations localized in the central nervous system in a mouse model of multiple sclerosis
Biography
Biography: Maha Bakhuraysah
Abstract
Despite clear evidence demonstrating that the deletion of Nogo-receptor 1 (NgR1) can protect against axonal degeneration and thus progression of experimental autoimmune encephalomyelitis (EAE), an immunological role for this receptor is yet to yield mechanistic evidence. However, recently NgR has been suggested as an alternate receptor for the B-cell activating factor (BAFF) in the central nervous system (CNS). Therefore, our strategic aim was to define whether NgR contributes in the modulation of the adaptive immune response during EAE by promoting maturation and differentiation of BAFF-reactive B-cells within follicles during the induction of disease. The results showed that CNS-infiltrating blood cells revealed an augmented response in the B-cells, which expressed NgR1 and NgR3, observed in ngr1+/+ mice with the onset and progression of the disease that could not be demonstrated within the spinal cords of EAE-induced ngr1-/- mice. Remarkably, a cluster of B-cells-expressing NgR was present at the meninges of lumbosacral spinal cords of the of ngr1+/+ EAE-induced mice at clinical score 1. Furthermore, there were significant increases of secreted immunoglobulins from these NgR1-expressing B-cells. Importantly, these cells could be directed into the synthesis phase of the cell cycle, after stimulating sorted cells by extracellular BAFF in vitro; however, when BAFF signaling was blocked using either rBAFF-R, or NgR1-Fc, or NgR3 peptides, the cells were observed to be into G0/G1 phase. As a consequence, when we blocked NgR1-ligand signaling using a novel hematopoietic stem cell-based delivery of a therapeutic protein, immune lineage-differentiated cells, including ZsGreen and fusion protein, were trafficking into the CNS during acute EAE. Collectively, these data indicate that the existence of an inducible expression of NgR1 and NgR3 in specific immune lineage cells upon the induction of EAE, and that the follicular-like NgR1 and NgR3-positive B-cells in the meninges may play an active role during the induction of EAE. Thus, our data reinforce the idea that blocking the interaction of BAFF and NgR1 and NgR3 may be vital for neuroprotection during inflammatory insults.