B and T cells are different types of immune cells with specific roles in the body. Debate has raged over which ones go awry in MS, however, a new study highlights a role for both of them in MS.
The key MS risk gene HLA-DR may be crucial for signalling between B and T cells. The immune system is like a well-oiled military force, having multiple branches just like a conventional military – with land, air and sea forces each with their own role to play. In the immune system these branches are the B cells and the T cells, and these two branches can be further broken down into more specialised groups.
In MS, this military juggernaut mistakes parts of the body as foreign invaders and attacks. How this happens is not overly clear, and considerable research has gone into trying to find out what gets misaligned for the immune system to converge and attack the brain and spinal cord.
Interestingly a number of the 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, helping recruit the rest of the immune system to fight the invader.
One cell that does this is a B cell, once a B cell finds an invader it breaks it up and displays it on its cell surface, using HLA-DR genes, showing the rest of the immune system what to attack. 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. But what role do each of the cell types have? And how does this lead to MS?
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, where there is no invader to attack. They showed that people with MS were more likely to have immune cells which were active and growing, and this was greater 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 and found that about 25% of these cells were B cells and about 45% of the cells were T cells. To see what role the B cells had, they removed them experimentally and looked at the effects on the T cells. They showed that the B cells were signalling to the T cells to be active, almost like they were telling them that the body is under attack – even though no infection was present.
They also showed that immune cells which had a lot of the MS gene HLA-DR were more likely to be active and proliferating. This gene is found on B cells and helps signal to T cells to make them active. The scientists blocked this signal and were able to block the activation of the T cells, showing one way in which this risk gene is playing a role.
Since there was no infection, the question remained of what the immune cells were targeting in their attack. Using cutting edge technologies to examine the proteins on the surface of T cells, the scientists demonstrated that these activated T cells in the blood were recognising protein structures produced by B cells as well as by 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 call in all the 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 into 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, it may be like disrupting the communications of the different branches of a military operation, preventing the coordinated attack that leads to MS.