# Role of B cell interactions in CNS autoimmune demyelination

> **NIH NIH R21** · UNIVERSITY OF IOWA · 2021 · $193,125

## Abstract

PRJOECT ABSTRACT
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous
system (CNS) whereby infiltrating autoreactive clones, with additional pro-inflammatory cell types
they recruit and support, work to destroy the protective myelin sheaths surrounding neurons. This
results in compromised nerve conduction and myriad pathologies including pain, vision loss,
cognitive deficits, and eventual paralysis. It is currently incurable. Due to its early life onset
(typically in the third or fourth decade) and that it progressively worsens over time, an MS
diagnosis tragically sentences patients to a prolonged battle, representing a significant health and
financial burden for nearly 1 million Americans. Understanding the complex immune cell interplay
governing pathogenesis and regulation of disease is critical for the discovery of novel therapeutics
for patients. The MS mouse model experimental autoimmune encephalomyelitis (EAE) has
provided great insights into these processes, and has focused on CD4 T cells (CD4s), which can
adoptively transfer paralysis to healthy mice. The role of B cells and CD8 T cells (CD8s) have
been understudied in comparison. Targeted B cell-depletion success in recent MS clinical trials
has renewed intense interest in the role these cells play in demyelinating disease. However, most
EAE models do not account for pathogenic B cells, where myelin peptide-induced models (eg.
MOG35-55) exhibit EAE in B-less mice. Full-length recombinant human MOG (hMOG) protein
induces B cell-dependent EAE but its production is biochemically cumbersome, time-consuming,
and expensive, representing a barrier of access to efficient investigation of B cells in EAE.
Additionally, MOG is a minor component and buried within the myelin structure and rodent MOG
has residue differences with human MOG that render its induced EAE B cell-independent. Myelin
proteolipid protein (PLP) in contrast is the most abundant myelin protein and shares 100% amino
acid sequence homology between mouse and human. However, like MOG35-55, PLP178-191 induces
B cell-independent EAE. We therefore designed a novel peptide encompassing the extracellular
domains of PLP and have found that it drives a robust B cell-dependent EAE. Our group has
demonstrated that myelin-specific CD8s in human PBMC have regulatory function and are
defective at inhibiting CD4s in MS patients. Further, PLP178-191-specific CD8s suppress EAE and
even eliminate paralysis in mice. Thus, B cell interactions with pathogenic CD4s and regulatory
CD8s (direct or through TFH cells) can be studied in our novel model. This PLP-driven, B cell-
dependent murine model of MS will be developed in the proposed work, and will not only advance
the field’s technical capability, but serve as a much-needed arena for investigating B cells in EAE.

## Key facts

- **NIH application ID:** 10105656
- **Project number:** 1R21AI156123-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Alexander Boyden
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $193,125
- **Award type:** 1
- **Project period:** 2021-03-10 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105656

## Citation

> US National Institutes of Health, RePORTER application 10105656, Role of B cell interactions in CNS autoimmune demyelination (1R21AI156123-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10105656. Licensed CC0.

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