New explanation for the cause of MS

In multiple sclerosis (MS), not only the T cells of the immune system, but also its B cells, play an important role. This is shown by researchers at Karolinska Institutet and the University of Zurich in a study published in the journal Cell. The findings explain how a new class of MS drugs works, and can open up for more precise ways of treating the disease.

MS is a chronic disease where the body's immune cells attack and damage its own nerve tissue. The disease affects around 2.5 million people worldwide, with a higher risk among women.

Now, a key aspect in the development of the disease has been found by researchers at Karolinska Institutet and the University of Zurich. The results are published in the journal Cell. Faiez Al Nimer, researcher at the Department of Clinical Neuroscience at KI, is co-first author of the study.

Attack the nerve cells

Until recently, MS research has mainly focused on a type of immune cells called T cells. They normally help protecting the body against intruders. In some people, however, they attack the protective layer surrounding the nerve cells – marking the onset of MS. The new study shows that not only T cells, but also B cells of the immune system, play a role in the development of the disease, by activating the T cells.

By analysing blood samples, the researchers saw that blood from people with MS contained increased numbers and activation status of T cells known to be important for MS disease activity. When the B cells were eliminated, the activation status of these disease-driving T cells returned to normal, suggesting that B cells play a crucial role in the activation of autoimmune T cells in MS.

Migrate to the brain

The team also discovered that these activated T cells detectable in the blood notably included those that also occur in the brain in MS patients during flare-ups of the disease. These T cells were shown to recognise the structures of a protein that is produced by the B cells as well as nerve cells in the brain. The researchers conclude that after being activated in the blood by B cells, the T-cells migrate to the brain, where they destroy the nerve tissue.

The study explains the previously unclear mechanism of a new class of MS drugs (rituximab and ocrelizumab) and can, according to researchers, pave the way for more precise ways of treating MS in the future.

The research is funded mainly by the European Research Council (ERC Advanced Grant). Further funds come from the University of Zurich, the Swiss Multiple Sclerosis Society, the Swiss National Science Foundation and a number of Swedish funding sources.

This news article is based on a press release from the University of Zurich.

Publication

"Memory B Cells Activate Brain-Homing, Autoreactive CD4 + T Cells in Multiple Sclerosis"
Ivan Jelcic, Faiez Al Nimer, Jian Wang, Verena Lentsch, Raquel Planas, Ilijas Jelcic, Aleksandar Madjovski, Sabrina Ruhrmann, Wolfgang Faigle, Katrin Frauenknecht Clemencia Pinilla, Radleigh Santos, Christian Hammer, Yaneth Ortiz, Lennart Opitz, Hans Grönlund, Gerhard Rogler, Onur Boyman, Richard Reynolds, Andreas Lutterotti, Mohsen Khademi, Tomas Olsson, Fredrik Piehl, Mireia Sospedra, and Roland Martin
Cell, online 30 August 2018, doi: 10.1016 / j.cell.2018.08.011