B Cells in the Spotlight: How Ocrelizumab Is Changing the Story of Multiple Sclerosis

For decades, multiple sclerosis (MS) was thought of primarily as a T-cell-driven immune-mediated disease. T cells, the “generals” of the immune system, were believed to orchestrate the attack on the brain and spinal cord that causes inflammation, demyelination, and neurodegeneration. But in recent years, researchers have discovered that another group of immune cells—B cells—play a much bigger role in MS than anyone expected. And with that realization came one of the most exciting advances in MS therapy: the development of drugs that target and deplete B cells.

Among these, ocrelizumab has made history. Not only does it effectively reduce relapses and MRI-detected inflammation in relapsing-remitting MS (RRMS), but it also became the first-ever therapy to slow disability progression in primary progressive MS (PPMS), a form of the disease that previously had no proven treatment.

So how did we get here, and what does this mean for people living with MS? Let’s unpack the story.

Why B Cells Matter in MS
B cells are more than just antibody factories. In MS, they:

Release pro-inflammatory signals (cytokines),

Present antigens to T cells, fueling immune attacks,

And, in some cases, cluster into structures in the brain’s meninges, where they may contribute to local damage.

In fact, about 90% of people with MS have telltale oligoclonal bands—antibodies made by B cells—detectable in their cerebrospinal fluid. This pointed researchers toward the idea that eliminating B cells could calm down the inflammatory storm in MS.

Meet the CD20-Targeting Antibodies
B cells carry a protein on their surface called CD20. Drugs designed to latch onto this protein can trigger the destruction of these cells while leaving most plasma cells (the long-lived antibody producers) intact. This means patients can achieve powerful suppression of inflammation without completely losing their protective antibodies against infections.

Three CD20-targeting therapies have been studied in MS so far:

Rituximab
Originally developed for lymphoma, rituximab was the first anti-CD20 antibody to be tested in MS. In clinical trials, it dramatically reduced relapses and brain lesions in RRMS. While it’s not officially approved for MS, rituximab has been widely used off-label, especially in Scandinavia, with strong real-world results.

Ocrelizumab
Ocrelizumab is a humanized antibody, designed to be less immunogenic and longer-lasting than rituximab. In large, rigorous phase III trials, it reduced relapse rates by nearly half compared to interferon-beta, cut MRI lesion activity by over 90%, and increased the percentage of patients achieving “no evidence of disease activity” (NEDA).

But the real breakthrough came in PPMS: for the first time, a therapy significantly slowed disability progression and brain volume loss. While the effect was modest, it offered hope to a patient group that previously had none.

Ofatumumab
A fully human anti-CD20 antibody, ofatumumab can be delivered via subcutaneous injection rather than infusion. Early studies show promising efficacy, and phase III head-to-head trials against teriflunomide are ongoing.

Safety and Practical Considerations

Like any powerful therapy, B-cell-depleting drugs come with risks:

Infusion reactions are common, especially with the first dose. Premedication with steroids and antihistamines helps.

Infections can occur, though rates in trials were not significantly higher than controls. Screening for hepatitis B is essential, and vigilance for rare complications like PML is needed.

Malignancy: In ocrelizumab trials, there was a numerical imbalance in breast cancer cases. While the overall risk is uncertain, standard cancer screening is advised.

Pregnancy: Because B cells play a role in fetal immune development, these drugs should generally be avoided during pregnancy.

Looking Forward
Anti-CD20 therapies represent a true milestone in MS care. For RRMS, they provide some of the most potent suppression of disease activity we’ve ever seen. For PPMS, they finally break the therapeutic stalemate.

Still, important questions remain:

How long should patients stay on therapy?

Can earlier use change the long-term trajectory of MS?

Will long-term treatment carry hidden risks, like malignancy?

And might combining B-cell depletion with other strategies (like remyelination-promoting therapies) yield even greater benefits?

For now, though, the success of ocrelizumab marks a new era. By shining the spotlight on B cells, researchers have not only unlocked a powerful treatment strategy but also deepened our understanding of MS itself. For patients and families facing this challenging disease, that’s a breakthrough worth celebrating.

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:
Gelfand, J.M., Cree, B.A.C. & Hauser, S.L. Ocrelizumab and Other CD20+ B-Cell-Depleting Therapies in Multiple Sclerosis. Neurotherapeutics 14, 835–841 (2017). https://doi.org/10.1007/s13311-017-0557-4