1. B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF
- Author
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Michael F. Azari, Fabienne Mackay, Paschalis Theotokis, John-Paul Abou-Afech, Amani A Alrehaili, Steven Petratos, Nikolaos Grigoriadis, Frank Alderuccio, Jae Young Lee, Christopher Siatskas, Maha M Bakhuraysah, Stephen M. Strittmatter, Pei-Mun Aui, and William A. Figgett
- Subjects
Cell signaling ,Encephalomyelitis, Autoimmune, Experimental ,Multiple Sclerosis ,Nogo Receptors ,Nogo Proteins ,Science ,Neuroimmunology ,Article ,Mice ,Myelin ,Meninges ,Immune system ,immune system diseases ,Nogo Receptor 1 ,B-Cell Activating Factor ,medicine ,Animals ,Humans ,B-cell activating factor ,Neuroinflammation ,Mice, Knockout ,B-Lymphocytes ,Multidisciplinary ,Chemistry ,Experimental autoimmune encephalomyelitis ,Cell cycle ,medicine.disease ,medicine.anatomical_structure ,Cancer research ,Diseases of the nervous system ,Medicine ,Female ,Neuroscience - Abstract
We have previously reported evidence that Nogo-A activation of Nogo-receptor 1 (NgR1) can drive axonal dystrophy during the neurological progression of experimental autoimmune encephalomyelitis (EAE). However, the B-cell activating factor (BAFF/BlyS) may also be an important ligand of NgR during neuroinflammation. In the current study we define that NgR1 and its homologs may contribute to immune cell signaling during EAE. Meningeal B-cells expressing NgR1 and NgR3 were identified within the lumbosacral spinal cords of ngr1+/+ EAE-induced mice at clinical score 1. Furthermore, increased secretion of immunoglobulins that bound to central nervous system myelin were shown to be generated from isolated NgR1- and NgR3-expressing B-cells of ngr1+/+ EAE-induced mice. In vitro BAFF stimulation of NgR1- and NgR3-expressing B cells, directed them into the cell cycle DNA synthesis phase. However, when we antagonized BAFF signaling by co-incubation with recombinant BAFF-R, NgR1-Fc, or NgR3 peptides, the B cells remained in the G0/G1 phase. The data suggest that B cells express NgR1 and NgR3 during EAE, being localized to infiltrates of the meninges and that their regulation is governed by BAFF signaling.
- Published
- 2021