# The Role of B cells in the Origin and Progression of Multiple Sclerosis

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $1,129,237

## Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system affecting nearly one
million individuals in the United States. The disease is characterized by acute and chronic inflammation, myelin
loss; oligodendrocyte, neuronal and axonal pathology; and progressive neurological dysfunction. A number of
breakthrough translational discoveries, and especially the highly beneficial effects of B cell depleting drugs, have
set the stage for a growing, yet still imperfect, therapeutic pipeline. Research will fall short of its potential to
improve patient outcomes until the trigger(s) of disease onset and modifiers of progression are identified.
Central to this project is the hypothesis that B cells presenting in the cerebrospinal fluid (CSF) and peripheral
blood during early MS play key roles in triggering MS and in mediating ongoing progressive disease activity. We
propose to interrogate unique patient cohorts, including an incident cohort, with novel enabling technologies to
identify triggers of MS and modifiers of the clinical course. Well characterized clinical populations, high-field
serial magnetic resonance imaging (MRI), genetic information organized as functional operational networks, and
a focus on B cell biology are the central elements of this initiative. A primary goal will be to characterize the
molecular diversity of B cells and their receptors at various stages of disease to identify pathogenic populations
and their antigenic targets.
A multi-layered experimental strategy includes single cell B cell transcriptomics, together with comprehensive
phage-displayed synthetic human, viral and microbial peptidomes for the screening of antibody fingerprints
against external drivers in the serum, CSF, and recombinant antibody libraries. The integrative analysis will
contextualize the data using clinical, MRI and genetic determinants, striving to apply rigorous statistical
principles, including independent replication.

## Key facts

- **NIH application ID:** 10401443
- **Project number:** 5R35NS111644-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** STEPHEN L HAUSER
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,129,237
- **Award type:** 5
- **Project period:** 2019-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401443

## Citation

> US National Institutes of Health, RePORTER application 10401443, The Role of B cells in the Origin and Progression of Multiple Sclerosis (5R35NS111644-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10401443. Licensed CC0.

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