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Author Spotlight: Creating a Versatile Experimental Autoimmune Encephalomyelitis Model Relevant for Both Male and Female Mice
Published on: October 13, 2023
Multiple Sclerosis-Like Symptoms in Mice Are Driven by Latent γHerpesvirus-68 Infected B Cells
Ana Citlali Márquez1, Iryna Shanina1, Marc Steven Horwitz1
1Department of Microbiology and Immunology, The University of British Columbia, Vancouver, BC, Canada.
Abstract:
Multiple sclerosis (MS) is caused by a combination of genetic and environmental factors. It is believed that previous infection with Epstein Barr Virus (EBV) plays an important role in the development of MS. Previously, we developed a murine model where latent infection with gamma herpesvirus 68 (γHV-68), a murine homolog to EBV, enhanced the symptoms of experimental autoimmune encephalomyelitis (EAE), resulting in disease that more closely resembles MS in humans. Here, we explored the conditions that were necessary for EAE enhancement. We showed that latently infected CD19+IgD- B cells were capable of enhancing EAE symptoms when transferred from mice previously infected with γHV-68 into uninfected mice. We also observed a prevention of enhancement when B cells were depleted before infection. However, depletion after the establishment of latency only partially reduced EAE. This indicated the existence of a mechanism where B cells play an important role as antigen presenting cells (APCs) prior to EAE induction for the priming of Th1 cells. It is possible that these signals persist even after B cell depletion, strongly suggesting a paracrine signaling modulation of non-B cell APCs. These results strongly support the concept that EBV contributes to the development of autoimmunity and highlights the need for a vaccine against EBV that could limit or prevent multiple sclerosis development.
Insights
Latent Epstein Barr Virus (EBV) infection enhances multiple sclerosis (MS) symptoms. Latently infected B cells are key drivers, acting as antigen-presenting cells that prime T-helper 1 cells, suggesting EBV vaccination could prevent MS.
Area of Science:
- Immunology
- Neuroscience
- Virology
Background:
- Multiple sclerosis (MS) pathogenesis involves genetic and environmental factors, with Epstein Barr Virus (EBV) infection implicated.
- A murine model using gamma herpesvirus 68 (γHV-68), an EBV homolog, replicates MS-like symptoms in experimental autoimmune encephalomyelitis (EAE).
Purpose of the Study:
- To investigate the specific conditions and cellular mechanisms underlying γHV-68-induced EAE enhancement.
- To determine the role of B cells in the exacerbation of autoimmune neuroinflammation.
Main Methods:
- Transfer of latently γHV-68 infected B cells into naive mice.
- B cell depletion before and after γHV-68 infection.
- Assessment of EAE severity and T-helper cell responses.
Main Results:
- Latently infected B cells transferred from γHV-68 infected mice enhanced EAE symptoms in recipient mice.
- Depletion of B cells prior to infection prevented EAE enhancement.
- Depletion after latency establishment only partially reduced EAE, suggesting persistent signaling.
Conclusions:
- B cells are crucial antigen-presenting cells (APCs) for priming Th1 cells, contributing to MS-like disease enhancement.
- Persistent paracrine signaling from B cells may modulate non-B cell APCs, maintaining autoimmune responses.
- Targeting EBV infection, potentially through vaccination, may be a strategy to prevent or limit MS development.
