# Molecular profiling of exosomes from multiple sclerosis B cells

> **NIH NIH R21** · WAYNE STATE UNIVERSITY · 2020 · $447,003

## Abstract

Project Summary/Abstract
B cells are central to the pathogenesis of multiple sclerosis (MS), including B cell functions unrelated to
production of immunoglobulins (Ig). Injury to gray matter (GM), particularly subpial GM, is a pathologic
substrate of the progressive stages of MS, with cognitive and physical worsening experienced by many
patients. Our hypothesis is that B cells from the peripheral immune system enter the spinal fluid and
meninges, and release non-immunoglobulin (Ig) factors that injure oligodendroglia (OL) and neurons/axons in
underlying cerebral cortical gray matter (GM) and slowly evolving perivascular lesions. Our research teams at
Wayne State University and the University of Pennsylvania are collaborating to investigate this hypothesis.
Supernatants (Sup) obtained from cultures of circulating B cells from MS patients are cytotoxic to both OL and
neurons in vitro; those from normal controls (NC) show little or no toxicity (Lisak et al. 2012, 2017). Killing is
independent of complement, and does not correlate with Sup levels of IgG, IgM or any single or combination of
a large number of soluble cytokines and other proteins. Death of OL and neurons involves apoptosis and is
caused by one or more factors in the >300 kDa fraction of MS B cell Sup (Lisak et al. 2017). We recently
discovered that the OL toxicity is found in exosome-enriched (Ex-En) extracellular vesicles (EVs) released by
the B cells from patients with MS (Benjamins et al. 2019). We will identify candidate factor/s using proteomics,
RNASeq and lipidomics. Blocking the production or action of the factor/s could decrease OL and neuronal
damage in cortical MS lesions and thus prevent progressive disease and enhance capacity for remyelination
and axonal protection. Anticipated new outcomes include (1) comprehensive molecular profiling and
characterization of Ex-En EVs released by MS B cells, which has not been done before, and (2)
identification of factors in or on the Ex-En EVs that could mediate the damage induced by B cells in
cortical lesions in MS. The integrated multiple -omics approaches we propose will generate rich datasets that
will provide insight into the fundamental biology of B cell EVs as well as the differences in B cell EV phenotype
and function in MS patients compared to NC. This project is significant because of its strong potential for
identifying new targets and strategies to decrease damage and promote repair of the CNS in patients with MS.
This B cell toxicity may be particularly relevant to non-relapsing progressive pathophysiology – a major unmet
therapeutic need. Our project is innovative because the function, components and roles of Ex-En EVs
released by MS B cells have not been previously investigated.

## Key facts

- **NIH application ID:** 10040973
- **Project number:** 1R21NS118227-01
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** AMIT BAR-OR
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $447,003
- **Award type:** 1
- **Project period:** 2020-07-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10040973

## Citation

> US National Institutes of Health, RePORTER application 10040973, Molecular profiling of exosomes from multiple sclerosis B cells (1R21NS118227-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10040973. Licensed CC0.

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