Journal Article

B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF

Azari, Michael F., Lee, Jae Young, Mackay, Fabienne, Strittmatter, Stephen M., Siatskas, Christopher, Bakhuraysah, Maha M., Petratos, Steven, Alrehaili, Amani A., Grigoriadis, Nikolaos, Abou-Afech, John-Paul, Aui, Pei-Mun, Theotokis, Paschalis, Alderuccio, Frank, Figgett, William A.

2021

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/378 / 631/378/1689 / 631/378/371 / Animals / B-Cell Activating Factor - metabolism / B-Lymphocytes - immunology / B-Lymphocytes - metabolism / BLyS protein / Cell cycle / Cell signaling / Central nervous system / DNA biosynthesis / Dystrophy / Encephalomyelitis, Autoimmune, Experimental - immunology / Encephalomyelitis, Autoimmune, Experimental - pathology / Experimental allergic encephalomyelitis / Female / G1 phase / Humanities and Social Sciences / Humans / Immunoglobulins / Inflammation / Lymphocytes B / Meninges / Meninges - immunology / Meninges - pathology / Mice / Mice, Knockout / multidisciplinary / Multiple Sclerosis - immunology / Multiple Sclerosis - pathology / Myelin / Nogo protein / Nogo Proteins - metabolism / Nogo Receptor 1 - genetics / Nogo Receptor 1 - metabolism / Nogo Receptors - metabolism / Peptides / Science / Science (multidisciplinary)