How Glatiramer Acetate Rewires B Cells to Calm Multiple Sclerosis

For decades, multiple sclerosis (MS) research has focused heavily on T cells—the immune warriors gone rogue, mistakenly attacking the central nervous system. But in recent years, B cells have stepped into the spotlight. Therapies that deplete B cells, such as anti-CD20 antibodies, have proven highly effective in controlling MS, highlighting just how central these cells are to disease progression.

Now, a fascinating study by Häusler and colleagues (2020) takes a closer look at another established MS therapy, glatiramer acetate (GA), and its surprisingly powerful effects on B cells.

A Quick Refresher: What is Glatiramer Acetate?
GA is a synthetic mixture of four amino acids—glutamic acid, lysine, alanine, and tyrosine. It’s been a mainstay in MS treatment for decades, known for reducing relapses and slowing disability progression. Traditionally, GA has been thought of as a T cell–modulating drug, shifting the immune system toward anti-inflammatory Th2 and regulatory T cell (Treg) responses.

But the exact mechanisms behind its benefits have never been fully clear. Could GA also work through B cells?

The Study: Looking Beyond T Cells
The researchers conducted a cross-sectional and longitudinal analysis of MS patients treated with GA compared to untreated patients. They also performed mouse experiments in experimental autoimmune encephalomyelitis (EAE)—the classic animal model of MS.

The central question:

Does GA change how B cells behave, particularly in their role as antigen-presenting cells (APCs)?

Key Findings
1. GA Shifts B-Cell Subsets
Fewer transitional B cells (immature cells) and plasmablasts (antibody-producing precursors).

A reduction in circulating B-cell frequency overall.

This suggests GA helps normalize B-cell differentiation, reducing the presence of highly activated, potentially pathogenic B-cell types.

2. GA Tames Pro-Inflammatory Signals
GA-treated B cells produced less TNF-α (a potent inflammatory cytokine).

They secreted more IL-10, a key anti-inflammatory molecule.

In short, B cells on GA look a lot less like inflammatory troublemakers and more like peacekeepers.

3. GA Boosts Antigen Presentation—But in a Good Way
GA increased MHC class II expression on B cells, a molecule crucial for presenting antigens to T cells.

Surprisingly, instead of fueling inflammation, GA-treated B cells promoted the expansion of regulatory T cells.

Meanwhile, the development of harmful Th1 and Th17 cells (both linked to MS flares) was reduced.

This flips the script: GA doesn’t just suppress B-cell activity—it reshapes B-cell–T-cell interactions to favor regulation over inflammation.

4. In Animal Models: Less Disease, More Balance
In EAE mice, GA treatment:

Reduced disease severity.

Dampened B-cell activation markers.

Increased Treg development.

This reinforces the human findings: GA calms the immune storm by nudging B cells into a more tolerogenic role.

Why This Matters
These results expand our understanding of GA’s therapeutic reach. Instead of acting solely through T cells, GA also reprograms B cells to act as allies rather than aggressors.

This could have several important implications:

MS therapy sequencing: After potent B-cell–depleting therapies like anti-CD20 antibodies, GA might serve as a maintenance therapy that encourages repopulating B cells to behave in a regulatory, not inflammatory, way.

Other autoimmune diseases: Since B cells are central players in diseases like neuromyelitis optica (NMO), GA’s B-cell–modulating abilities may extend beyond MS.

Personalized medicine: Patients with high baseline B-cell frequencies seemed less responsive to GA, suggesting that B-cell profiling could one day guide treatment choices.

Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.

References:
Yu K, Jiang R, Li Z, Ren X, Jiang H, Zhao Z. Integrated analyses of single-cell transcriptome and Mendelian randomization reveal the protective role of FCRL3 in multiple sclerosis. Frontiers in Immunology (Published July 15, 2024).