B Cells: Rethinking How MS Treatments Work
When most people hear about multiple sclerosis (MS), they think of it as a disease driven by T cells, the immune system’s powerful foot soldiers. For decades, research and therapies have focused heavily on this arm of immunity. But new work is revealing a surprising twist: B cells—the immune cells better known for making antibodies—are also major players in the MS story.
A study led by James Dooley and colleagues at KU Leuven and published in Neurology: Neuroimmunology & Neuroinflammation (2016) takes a deep dive into this question. Using a systems immunology approach, the team mapped out the immune profiles of patients with MS, comparing untreated individuals, those receiving four common therapies, healthy controls, and even patients with autoimmune thyroid disease (AITD). Their findings spotlight early B cell changes as a shared pathway of treatment response, shaking up long-held assumptions about MS and its therapies.
A Systems Immunology Approach to MS
Studying the immune system in all its complexity is tricky. Narrow studies often zoom in on one or two cell types, but MS is a multifaceted disease. Dooley and colleagues sidestepped this limitation by using comprehensive flow cytometry, measuring 38 different immune cell populations in the blood of 245 individuals.
This large-scale analysis included:
154 MS patients (treated and untreated)
55 patients with autoimmune thyroid disease (AITD), a useful comparison given its shared genetic risk with MS
36 healthy controls
This “panoramic” immune view revealed striking patterns that wouldn’t have been visible if researchers had focused only on T cells.
Untreated MS: A Landscape of Memory Cells
In untreated MS patients, the immune system showed two standout features:
Increased effector memory CD8+ T cells – a type of T cell primed for rapid attack.
Increased memory B cells – long-lived B cells ready to respond quickly to antigens.
Interestingly, while AITD patients also showed immune alterations, the patterns were different. Despite shared genetic risks, MS and AITD produced distinct immune “signatures,” suggesting each autoimmune disease has its own unique immune architecture.
What Happens When Treatments Enter the Picture?
The researchers then looked at four common MS therapies:
Interferon-beta (IFN-β)
Fingolimod
Natalizumab
Glatiramer acetate
Surprisingly, the biggest immune shifts were linked to B cells rather than T cells.
Interferon-beta and fingolimod triggered broad changes in the immune system. Despite their differences, they shared two striking effects:
An increase in transitional B cells (immature B cells just leaving the bone marrow)
A decrease in class-switched B cells (mature B cells specialized in producing potent antibodies)
These changes were closely tied to levels of B cell-activating factor (BAFF), a protein that fuels B cell survival and development. BAFF levels rose in patients on both therapies, pointing to a shared mechanism of action.
By contrast, glatiramer acetate and natalizumab produced only modest or inconsistent immune shifts in this dataset.
Why B Cells Matter More Than We Thought
For years, MS was considered primarily a T-cell-driven disease. But the success of B-cell-depleting therapies (like rituximab and ocrelizumab) hinted that this wasn’t the full story. Dooley and colleagues add weight to this idea, showing that even therapies not designed to target B cells end up reshaping B cell populations.
Their findings suggest that the “early B cell pathway” is a critical shared target across effective MS therapies.
But BAFF, the protein at the heart of this process, may play a “double agent” role:
In autoimmune thyroid disease, high BAFF appears pathogenic, promoting disease.
In MS, BAFF upregulation during therapy seems protective, linked to beneficial immune remodeling.
This duality could explain why BAFF-blocking drugs (like atacicept) failed in MS trials and even worsened disease, despite promising animal data.
Implications for Future MS Treatment
The study highlights several key takeaways for MS research and care:
MS treatments converge on B cells. Even drugs thought to primarily act on T cells (like interferon-beta) show strong B-cell effects.
BAFF is central—but context matters. Blocking it may help in some autoimmune diseases, but in MS it seems essential for therapeutic benefit.
Personalized medicine is possible. By profiling immune signatures, clinicians may one day tailor therapies to patients based on their unique immune architecture.
A New Chapter in the MS Story
This study marks an important pivot in MS research. Instead of thinking about treatments as acting through mysterious or unrelated pathways, we now see a convergent theme: reshaping the B cell compartment.
It’s a reminder of the complexity—and adaptability—of the immune system. The same molecule (like BAFF) can be harmful in one disease and protective in another. And the immune “villains” we once overlooked, like B cells, may turn out to be central to both disease and therapy.
For patients and clinicians, this research opens the door to more targeted, personalized, and effective treatment strategies—and offers hope that future therapies will continue to unravel the intricate web of MS immunology.
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:
Dooley, J., Pauwels, I., Franckaert, D., Smets, I., Garcia-Perez, J. E., Hilven, K., ... & Goris, A. (2016). Immunologic profiles of multiple sclerosis treatments reveal shared early B cell alterations. Neuroimmunology & Neuroinflammation, 3(4), e240.
