# Defining the role of B cells in modulating CNS inflammation in multiple sclerosis

> **NIH NIH F31** · GEORGE WASHINGTON UNIVERSITY · 2020 · $39,120

## Abstract

Summary
The debilitating central nervous system (CNS) disease multiple sclerosis (MS), is characterized by an influx of
peripheral immune cells that coincides with axonal demyelination and damage, resulting in pain and impaired
coordination. The role of B cells in MS pathogenesis has emerged as studies showed that B cell directed
therapies substantially reduce the formation of new inflammatory demyelinating lesions. Further, the majority of
lesions from patients with established MS harbor B cells as well as reactive microglia. While these findings
corroborate a pathogenic role for B cells, it is unclear which B cell function contributes to demyelination within
the inflamed CNS. In addition, systemic B cell elimination can severely immunocompromise patients,
establishing the need to develop more targeted therapies. Emerging evidence suggests that B cells of MS
patients are potent regulators of pro-inflammatory cytokines, and these abnormal B cells can regulate the CNS
innate immune system when they enter the CNS. Studies in this application will selectively and locally ablate B
cells in the CNS using a novel caspase 9-mediated apoptosis transgenic tool in the well-studied experimental
autoimmune encephalomyelitis (EAE) animal model of MS. Preliminary data indicate that targeting CNS B cells
after the onset of symptoms in EAE reduces microglial reactivity and is accompanied by decreased myelin
damage and functional impairment. Inflammatory signaling pathways in microglia from CNS B cell depleted
EAE animals will be evaluated using advanced phospho-flow cytometry techniques. Demyelination and
remyelination in the brain and spinal cord will be further studied in this powerful, novel animal model to test if
CNS B cell ablation prevents further myelin injury and promotes myelin repair. The role of MS B cells in
neuroinflammation will be determined by stimulating human microglia with MS patient-derived B cell secreted
factors and analyzing transcriptional and translational inflammatory activity of microglial cells. B cell induced
microglial activation will be confirmed in human MS brain lesions. Together, the proposed studies will provide
novel insights into the complex immunopathology of MS that involves the interaction of CNS B cells and
microglia. Completion of these studies will lead to novel immunomodulatory therapeutic avenues that reduce
the disease burden of multiple sclerosis without immunocompromising the patient.
The proposed training plan is sponsored by Dr. Robert H. Miller at the George Washington University School of
Medicine and Health Sciences. The overall goal is to build a strong foundation for the PI, Julie J Ahn, to
prepare her for a successful career as an independent scientist in the fields of neuroimmunology and
neuroinflammation. The fellowship training plan includes the following goals: 1) enhance scientific knowledge
and technical skills that integrate neuroscience and immunology, 2) present research findings through oral
pres...

## Key facts

- **NIH application ID:** 9992496
- **Project number:** 1F31NS117085-01
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Julie J Ahn
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,120
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992496

## Citation

> US National Institutes of Health, RePORTER application 9992496, Defining the role of B cells in modulating CNS inflammation in multiple sclerosis (1F31NS117085-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9992496. Licensed CC0.

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