Novel pathogenic B cell subsets driving tissue damage in MS.

B cells are specific cells of the immune system. Clinical studies have shown that the inactivation of B cells by anti-B cell treatments helps to improve the clinical state of patients with the inflammatory brain disease Multiple Sclerosis (MS). This means that B cells play an important role in the disease development of MS, although it is not exactly clear how this works. In MS brains, B cells, besides in the blood, are also present in the meninges, which are tissue layers that cover and protect the brain. In patients with MS, substances that are produced by these B cells are believed to contribute to the loss of myelin sheaths that surround the nerve cell processes. This loss of myelin sheaths, also called demyelination, is a typical sign of MS and results in loss of the nerve cells, a process that is called neurodegeneration. Especially this inflammation and the neurodegeneration in the outer layers of the brain become more obvious when MS patients grow older, a process that also is called inflammaging. We think that specific groups of B cells called 4BL B cells and T-bet pos. B cells play a specific role in this inflammaging in patients with MS. To proof that these cells are important in the regulation and pathology of MS we thus will invest whether and where these cells can be found in MS brains as compared to other brain diseases. We also will analyse the phenotype of these cells in the blood and in the brain of MS patients, meaning that we will identify which molecules these cells use to communicate with other cells of the immune system and how these molecules influence the pathological processes leading to the clinical disease. Further, we will use a mouse model of MS, so-called experimental autoimmune encephalitis, to further study the role of these cells. This will be done by investigating if and how the inflammatory response and the clinical disease in these animals changes after injection of these specific types of B cells. The results of these studies may be used to create novel therapeutic strategies, especially for older MS patients that have chronic MS.