B cells among factors leading to brain lesions in multiple sclerosis

September 4, 2018, University of Zurich
In multiple sclerosis, the immune system attacks the myelin sheaths of the nerve fibres (white). Credit: Ralwel/iStockphoto

A team of researchers from the University of Zurich and the University Hospital Zurich has shown that in multiple sclerosis it is not only specific T cells that cause inflammation and lesions in the brain. B cells, a different type of immune cell, also play a role. These cells activate T cells in the blood. This discovery explains how new MS drugs take effect, opening up novel options for treating the disease.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. The body's own attack and damage the layer that surrounds in the and spinal cord, which affects their ability to communicate with each other. The disease, which affects around 2.5 million people worldwide, is a common cause of disability in young adults and affects women particularly often. MS can lead to severe neurological disabilities such as sensory problems, pain and signs of paralysis.

A team led by neurologist Roland Martin and immunologist Mireia Sospedra at the University of Zurich (UZH), the University Hospital Zurich (USZ) and researchers at the Karolinska Institute in Sweden has now discovered a key aspect in the pathogenesis of MS. "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," says Roland Martin, Director of the Clinical Research Priority Program Multiple Sclerosis at UZH.

Until recently, MS research had mainly focused on T cells, or T . They are the immune system's "guardians", which for example sound the alarm if the organism is infected with a virus or bacteria. In about one in a 1,000 people, the cells' ability to distinguish between the body's own and foreign structures becomes disturbed. The effect of this is that the misguided T cells start to attack the body's own – the onset of MS. However, the T cells aren't the sole cause of this. "A class of MS drugs called Rituximab and Ocrelizumab led us to believe that B cells also played an important part in the pathogenesis of the disease," explains Roland Martin. These drugs eliminate B cells, which very effectively inhibits inflammation of the brain and flare-ups in patients.

The researchers established the role of B cells by using an experimental in-vitro system that allowed blood samples to be analyzed. The blood of people with MS revealed increased levels of activation and cellular division among those T cells attacking the body's myelin sheaths that surround nerve cells. This was caused by B cells interacting with the T cells. When the B cells were eliminated, the researchers found that it very effectively inhibited the proliferation of T cells. "This means that we can now explain the previously unclear mechanism of these MS drugs," says Roland Martin.

Moreover, the team also discovered that the activated T cells in the blood notably included those that also occur in the brain in MS patients during flare-ups of the disease. It is suspected that they cause the inflammation. Further studies showed that these T cells recognize the structures of a protein that is produced by the B cells as well as nerve cells in the brain. After being activated in the peripheral blood, the T migrate to the brain, where they destroy nerve tissue. "Our findings not only explain how new MS drugs take effect, but also pave the way for novel approaches in basic research and therapy for MS," concludes Roland Martin.

Explore further: Cellular self-digestion process triggers autoimmune disease

More information: Ivan Jelcic et al. Memory B Cells Activate Brain-Homing, Autoreactive CD4+ T Cells in Multiple Sclerosis, Cell (2018). DOI: 10.1016/j.cell.2018.08.011

Related Stories

Cellular self-digestion process triggers autoimmune disease

December 13, 2017
Autophagy refers to a fundamental recycling process of cells that occurs in yeast, fungi, plants, as well as animals and humans. This process allows cells to degrade their own components and thus activate energy resources ...

A molecular key for delaying the progression of multiple sclerosis is found

July 23, 2018
Multiple sclerosis (MS) is an autoimmune disease that attacks and destroys the myelin sheath that insulates nerve cells. Current treatment is based on modulating the activity of the immune system or preventing immune cells ...

Potential new approach to the treatment of multiple sclerosis

March 5, 2018
A prospective new method of treating patients with multiple sclerosis has been proposed by researchers of the Mainz University Medical Center working in cooperation with researchers of the University of Montreal. In model ...

Aggressive immune cells aggravate Parkinson's disease

July 20, 2018
Parkinson's disease, formerly referred to as "shaking palsy," is one of the most common disorders affecting movement and the nervous system. Medical researchers at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) ...

Identifying the dangers of chronic stress on multiple sclerosis

February 6, 2018
New research reveals how chronic stress and tiny brain inflammations cause fatal gut failure in a multiple sclerosis mouse model.

Researchers report novel complementary effects of estrogen treatment in multiple sclerosis

December 28, 2017
A study by UCLA researchers reveals the cellular basis for how the hormone estrogen protects against damage to the central nervous system in people with multiple sclerosis (MS). The researchers found that estrogen treatment ...

Recommended for you

When storing memories, brain prioritizes those experiences that are most rewarding

November 20, 2018
The brain's ability to preserve memories lies at the heart of our basic human experience. But how does the brain's mechanism for memory make sure we remember the most significant events and not clog our minds with superfluous ...

Can genetic therapy help kids with Angelman syndrome overcome seizures?

November 20, 2018
Angelman syndrome is a genetic disease with no cure. Children grow up with severe intellectual disabilities and a range of other problems, arguably the worst of which are epileptic seizures. Now scientists at the UNC School ...

To predict the future, the brain has two clocks

November 20, 2018
That moment when you step on the gas pedal a split second before the light changes, or when you tap your toes even before the first piano note of Camila Cabello's "Havana" is struck. That's anticipatory timing.

Researchers hope to be able to replace dysfunctional brain cells

November 20, 2018
A new study by researchers at Karolinska Institutet supports the theory that replacement of dysfunctional immune cells in the brain has therapeutic potential for neurodegenerative diseases like ALS and Alzheimer's disease. ...

White matter pathway and individual variability in human stereoacuity

November 20, 2018
Researchers in the Center for Information and Neural Networks (CiNet), the National Institute of Information and Communications Technology and Osaka University have identified a human white matter pathway associated with ...

New immunotherapy improves MS symptoms

November 20, 2018
A world-first clinical trial of a new cellular immunotherapy for multiple sclerosis (MS) has improved symptoms and quality of life for the majority of patients.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.