Infection and Activation of B Cells by Theiler's Murine Encephalomyelitis Virus (TMEV) Leads to Autoantibody Production in an Infectious Model of Multiple Sclerosis.

Young-Hee Jin,Jocelin Huang,Byung S Kim,Charles X Kim

doi:10.3390/cells9081787

Abstract

Theiler’s murine encephalomyelitis virus (TMEV) induces immune-mediated inflammatory demyelinating disease in susceptible mice that is similar to human multiple sclerosis (MS). In light of anti-CD20 therapies for MS, the susceptibility of B cells to TMEV infection is particularly important. In our study, direct viral exposure to macrophages and lymphocytes resulted in viral replication and cellular stimulation in the order of DCs, macrophages, B cells, and T cells. Notably, B cells produced viral proteins and expressed elevated levels of CD69, an activation marker. Similarly, the expression of major histocompatibility complex class II and costimulatory molecules in B cells was upregulated. Moreover, TMEV-infected B cells showed elevated levels of antigen-presenting function and antibody production. TMEV infection appeared to polyclonally activate B cells to produce autoantibodies and further T cell stimulation. Thus, the viral infection might potentially affect the outcome of autoimmune diseases, and/or the development of other chronic infections, including the protection and/or pathogenesis of TMEV-induced demyelinating disease.

Highlights

Infection with Theiler’s murine encephalomyelitis virus (TMEV) induces a chronic progressive demyelinating disease in susceptible mouse strains, such as SJL/J [1]
Autoantibody production was markedly accelerated in autoimmunity-prone mice following TMEV infection. These results strongly suggest that transient viral infection can induce a set of innate immune responses via toll-like receptor (TLR), which trigger the activation of B cells and antibody production, including autoantibodies, as well as triggering activation of pathogenic T cells
This information may be critically important in understanding the potential pathogenic mechanisms involved in TMEV-induced demyelinating disease, because this cell type is unique for both antibody production and T cell stimulation

Summary

Introduction

Infection with Theiler’s murine encephalomyelitis virus (TMEV) induces a chronic progressive demyelinating disease in susceptible mouse strains, such as SJL/J [1]. Infiltration of proinflammatory T cells is associated with tissue destruction and demyelination [4,5]. Studies have indicated that the level of Th1 responses during early viral infection is critically important in the protection from, rather than the pathogenesis of, the demyelinating disease [6,7]. Levels of antiviral antibody responses, as well as antiviral CD8+ T cell responses during the early stage of viral infection, play a crucial protective role [8,9,10], whereas their role in later stages of viral infection is less clear. Studies have indicated that Th17 CD4+ T cells are associated with the pathogenesis of TMEV-induced

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Results

Conclusion