Epstein Barr virus-immortalizedＢlymphocytes exacerbate experimental autoimmune encephalomyelitis in xenograft mice

Authors

Pascal Polepole, University of Nebraska - Lincoln
Alison Bartenslager, University of Nebraska - LincolnFollow
Yutong Liu, University of Nebraska Medical CenterFollow
Thomas M. Petro, University of Nebraska Medical CenterFollow
Samodha C. Fernando, University of Nebraska - LincolnFollow
Luwen Zhang, University of Nebraska - LincolnFollow

ORCID IDs

Luwen Zhang ORCID iD: 0000-0002-1621-8034

Document Type

Article

Date of this Version

7-2020

Citation

Pascal Polepole, Alison Bartenslager, Yutong Liu, Thomas M. Petro, Samodha Fernando, & Luwen Zhang (2020), Epstein Barr virus‐immortalized B lymphocytes exacerbate experimental autoimmune encephalomyelitis in xenograft mice. Journal of Medical Virology (advance publication 16 June 2020),

https://doi.org/10.1002/jmv.26188

Comments

Copyright 2020 John Wiley. Used by permission.

Abstract

Multiple sclerosis (MS) is the most common autoimmune disorder affecting the central nervous system. Epstein-Barr virus (EBV) is a causative agent for infectious mononucleosis (IM) that is associated with MS pathogenesis. However, the exact mechanism by which EBV, specifically in IM, increases the risk for MS remains unknown. EBV immortalizes primary B lymphocytes in vitro and causes excessive B lymphocyte proliferation in IM in vivo. In asymptomatic carriers, EBV-infected B lymphocytes still proliferate to certain degrees, the process of which is tightly controlled by the host immune systems. Experimental autoimmune encephalomyelitis (EAE) mimics key features of MS in humans and is a well-established rodent model for human MS. We have found that xenografts of EBV-immortalized B lymphocytes, which partially resemble the hyperproliferation of EBV-infected cells in IM, exacerbate autoimmune responses in myelin oligodendrocyte glycoprotein-induced EAE in C57BL/6 mice. After remission, an additional challenge with EBV-immortalized cells induces a relapse in EAE. Moreover, xenografts with EBV-immortalized cells tighten the integrity of blood brain barrier (BBB) in thalamus and hypothalamus areas of the mouse brains. Genomic sequences of prokaryotic 16S rRNA presented in feces reveal that EBV-immortalized cells significantly change the diversities of microbial populations. Our data collectively suggest that EBV-mediated proliferation of B lymphocytes may be a risk factor for the exacerbation of MS, which are associated with gut microbiome changes and BBB modulations. Furthermore, multiple xenografts of EBV-immortalized cells into in C57BL/6 mice could sever as a useful model for human relapsing-remitting MS with predictable severity and timing.