New multiple sclerosis culprit identified

It is still unclear what causes multiple sclerosis, but new research closes in on the faulty immune system mechanisms involved in the development of this condition.

Multiple sclerosis (MS), which is an autoimmune disease, causes the immune system to mistakenly attack myelin.

Myelin is the substance that coats axons, which are the projections that allow neurons to connect and transmit information.

This process is known as demyelination, and it affects the correct functioning of the central nervous system.

The condition is characterized by problems with balance and coordination, as well as with eyesight, to name but a few of its effects. In the United States, MS affects 250,000–350,000 people.

Researchers still don't know for sure what causes MS, but little by little, they are uncovering the mechanisms at play and revealing more of the cellular culprits involved.

Now, neurologist Roland Martin and immunologist Mireia Sospedra — at the University of Zurich and University Hospital Zurich, both in Switzerland — and colleagues have shown that a type of immune cell called B cells are key to the autoimmune reactions that characterize MS.

In a study whose results are now published in the journal Cell, the scientists explain that B cells influence the activity of another type of immune cell, T cells, which then cause inflammation.

"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

B cells influence T cells

Studies into MS will tend to focus on the role played by T cells in the development of this condition, since T cells are tasked with triggering an appropriate immune response once they detect the presence of pathogens.

When T cells malfunction and mistake healthy cells in the body for pathogens, this causes harmful lesions and inflammation, associated with autoimmune diseases such as MS.

Martin and colleagues, however, found that the T cells may actually be mistakenly activated by other specialized immune cells: the B cells.

This became apparent to the researchers after they observed the effects of certain drugs used to treat MS.

Martin says, "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."

These drugs, the authors note, halt brain inflammation by removing B cells, which suggests that these immune cells are ultimately responsible for the T cells' activity.

A chain of reactions

In order to better understand the role played by B cells in inflammation, the researchers analyzed blood samples from people with MS through an experimental in vitro method.

They noticed that B cells were interacting with specialized T cells, boosting their activity, and influencing them to divide more — thus feeding their attack cycle.

It became clear that B cells were the cause of T cell activity because, when they eliminated the former, the latter stopped proliferating.

"This means that we can now explain the previously unclear mechanism of these MS drugs," explains Martin.

The investigators also note that the activated T cells they studied in the blood samples include the population of T cells that are active in brain inflammation related to MS.

Martin and his team suggest that the T cells are able to read both the proteins released by B cells and recognize the nerve cells in the brain. The scientists say that T cells are first activated in the peripheral blood, only to migrate to the brain, where they end up attacking myelin.

"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," says Martin.