Interaction between immune cells may contribute to MS

MS research has not yet uncovered the role of different parts of the immune system in MS. However, in a new study, scientists have discovered a complex interaction between B and T cells that may contribute to MS.

The immune system is like a well-organised military force, with multiple branches (e.g. air, land and sea) each playing their own role. In the immune system, these branches are the B cells and the T cells, which can be further broken down into more specialised groups.

In MS, this military juggernaut mistakes parts of the body as foreign invaders and therefore attacks. How this happens is not fully understood and considerable research has taken place to find out precisely what becomes misaligned to cause the immune system to converge and attack the brain and spinal cord.

A number of MS risk genes are known to play a role in the immune system – in particular, one strong risk gene known as HLA-DR. This gene is used by a variety of immune cells to display targets for the immune system to attack. The cell displays the so-called invader on its cell surface, showing the rest of the immune system the target to attack and thereby equipping the immune system to fight the invader.

One type of cell that carries out this process is a B cell. Once a B cell finds an invader, it breaks it up and uses HLA-DR genes to display this invader on its cell surface.

Traditionally, B cells have been overlooked as the driving cells in MS. However, with the recent success of therapies targeting B cells such as Ocrevus, it has become clear that B cells also play an important role. Yet, questions remain around the exact role of each cell type and how these cell types lead to MS.

Immune cell study

In a recent study, published in the highly prestigious journal Cell, a group of scientists looked at the immune cells (both B and T cells) in the blood of people with and without MS and measured whether they were active and proliferating even in the absence of an infection (i.e. where there is no invader to attack). The results showed that people with MS were more likely to have immune cells that were active and growing and that this occurred to a greater degree than in people with other immune conditions, such as psoriasis or Crohn’s disease.

The scientists then looked at which type of immune cells were proliferating and appeared to be active. They found that about 25 per cent of these cells were B cells and about 45 per cent were T cells. To identify the role of the B cells, they removed them experimentally and examined the knock-on effect this had on the T cells. The results showed that the B cells were signalling to the T cells to be active, as if communicating to the T cells that the body was under attack, despite the fact that no infection was present.

The scientists also showed that immune cells that possessed a larger quantity of the MS gene HLA-DR were more likely to be active and proliferating. As mentioned above, HLA-DR is found on B cells and helps signal to T cells to make them active. When the scientists blocked this signal, they were able to block the activation of the T cells, showing one way in which this risk gene is playing a role.

Protein structures

Since there was no infection present, the scientists still faced the question of what exactly the immune cells were targeting in their attack. Upon examining the proteins on the surface of the T cells, the scientists demonstrated that these activated T cells in the blood were recognising protein structures produced by B cells as well as nerve cells in the brain. This potentially means that, when the T cells see this protein on B cells, they decide it is an enemy and signal to the entire immune system to mount an attack. Since the protein is produced by nerve cells, if these cells get into the brain, they will then recognise the same protein on brain cells and attack, thinking it is an enemy.

This is a hugely comprehensive study, which has delineated some of the roles of different cells and molecules of the immune system in MS. It links to the role of one of the major MS risk genes, and explains how the different forces of the immune system can interact to produce the immune response that is seen in MS. If we can block the coordination of the immune system, this may have a similar effect to disrupting the communications of the different branches of a military operation, thereby preventing the coordinated attack that leads to MS.

With thanks to MS Research Australia – the lead provider of research summaries on our website.