How B-cells Work to Promote T-cell Attacks on Myelin That Lead to MS Detailed in Study

How B-cells Work to Promote T-cell Attacks on Myelin That Lead to MS Detailed in Study

B-cells in the immune system play an important role in the unfolding of inflammation and brain lesions in multiple sclerosis (MS), largely by how they influence the actions of another immune system cell, called T-cells, a new study reports.

Its findings help explain why therapies like Ocrevus and off-label use of rituximab, both of which act on B-cells, are effective in controlling MS.

The study, “Memory B Cells Activate Brain-Homing, Autoreactive CD4+ T Cells in Multiple Sclerosis,” was published in the journal Cell.

Despite advances in understanding MS, it is still unclear exactly which specific cells and molecules drive the immune system to attack healthy tissue and damage the protective myelin layer surrounding nerve cells in the brain and spinal cord.

A team of researchers at the University of Zurich and the Karolinska Institute in Sweden report that memory B-cells, so-called because they normally work to remind the immune system of past threats so that such invaders (like viruses) are stopped quickly, also cause autoreactive T-cells to proliferate in MS patients. Once these cells reach the brain, they promote inflammation and demyelination (loss of myelin).

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That misguided T-cells are key players in attacks on the body’s nerve tissue in MS is well-known, but the study showed how B-cells are crucial to the damage done by these T-cells, the researchers said. 

“We were able to show for the first time that certain B-cells — the cells of the immune system that produce antibodies — activate the specific T-cells that cause inflammation in the brain and nerve cell lesions,” Roland Martin, MD, PhD, director of the Clinical Research Priority Program Multiple Sclerosis at University Hospital Zurich, said in a press release.

The team decided to investigate B-cells’ possible role in MS onset specifically because of Ocrevus (ocrelizumab), an approved therapy for both progressive and relapsing-remitting forms of MS, and the investigational therapy rituximab, both by Genentech. These two agents deplete B-cells that express a protein called CD20 on their surface with the aim of reducing MS flares and brain inflammation. (Rituximab is sold as  Rituxan in the U.S. and as MabThera in Europe to treat various types of blood cancer, and it is used as an off-label MS therapy.)

Researchers performed laboratory analyses using blood cells donated by relapsing-remitting MS patients and healthy people.

They saw excessive activity and proliferation by T-cells that attack nerve cells, and traced that excessiveness to B-cells interacting with T-cells. When B-cells were removed from the blood cells, T-cells essentially stopped proliferating.

“This means that we can now explain the previously unclear mechanism of these MS drugs,” Martin said, referring to Ocrevus and rituximab. 

Researchers also found T-cells activated by B-cells in the blood corresponded to those observed in the brains of MS patients during disease flares.

The team further identified a protein that is produced both by B-cells and nerve cells, and that works as a “bait” to make autoreactive T-cells recognize and turn against nerve cells.

“ These findings will be instrumental to address important questions regarding pathogenic B-T cell interactions in multiple sclerosis and possibly also to develop novel therapies,” the study concluded.

5 comments

  1. Cdf says:

    Question: if you had an overactive thyroid previously, and this is measured by your T4 blood cells, would their be and indication or thought, evidence of future diagnosis of MS?

    Since your thyroid glands purposes is regulating all aspects of your organs t cells & b cells? Awaiting your reply.

    • Cynthia King says:

      I don’t think so. It’s a hormone that the Thyroid test measure when they do T3&T4. Too much, hyperthyroid, too little hypothyroid. The also may look for antibodies present when you are hypothyroid, which classifies you as having another autoimmune disorder called Hashimoto’s thyroid whereby the immune system has destroyed the thyroid function. I am not a doctor and I have not been involved in healthcare in many years, so trust then google.

  2. Rex A. Hess says:

    This is an absolutely incredible study. It is this type of research data that opens the door for more precise targeting of therapies.

  3. Christopher T. says:

    Only problem is it’s only a fraction of what comprises MS. We’re still not close to understanding what causes this condition, or what exactly it is.

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