Researchers have found evidence that immune cells known as B cells from people with MS may produce toxic factors that harm brain cells, in particular, cells that make myelin, the key substance needed for nerve transmission. If this factor (or factors) can be identified and confirmed to play a role in MS disease progression, it may serve as an important target for developing new MS therapies. Robert Lisak, MD, and colleagues at Wayne State University (Detroit, MI) and collaborators in Montreal, Canada report their findings in the Journal of Neuroimmunology.
The study was supported by many sources including a National MS Society Collaborative MS Research Center Award, the Canadian Institutes of Health Research, and the MS Society of Canada.
Multiple sclerosis involves immune system attacks against the brain and spinal cord, particularly myelin (the substance that surrounds and supports nerve fibers). B cells are one type of immune cell, and one of their roles is to make and secrete antibodies, which are substances that fight off infection in healthy people but that also can cause disease. B cells are more active in the blood and brain of people with MS, and evidence suggests that they contribute to myelin damage in MS, although their exact role is unclear. In clinical trials, a therapy (rituximab) that targets B cells reduced MS relapses and brain lesions in people with MS, and this approach with a related drug is in clinical trials.
Dr. Lisak and colleagues obtained B cells from the blood of seven people with relapsing-remitting MS and four healthy controls. After growing the B cells in lab containers, they removed the cells and tested the culture medium (the liquid in which they grew), which allowed them to test the substances made by the B cells. They then isolated brain cells from rats, including oligodendrocytes, the cells that make myelin. They added the B cell culture medium to these cells and looked at the effects on the different types of brain cells. When they added B cell culture medium from people with MS, substantially more oligodendrocytes died than when they used B cell culture medium from healthy controls.
Moreover, following addition of the B cell culture medium from people with MS, the team observed changes in the appearance of other types of brain cells known to interact with oligodendrocytes in the brain. Thus, Dr. Lisak and colleagues concluded that B cells secrete a previously undescribed substance that appears to be toxic to oligodendrocytes, and does not appear to be an antibody. This toxic substance may directly impact the oligodendrocytes and/or indirectly impact these myelin-making cells through the actions of other cell types.
Although B cells and the substances they make and secrete are known to have detrimental effects on myelin, this study provides new insight into how these effects may occur. If the toxic substance (or substances) produced by B cells can be identified and confirmed to play a role in MS, it may serve as an important target for developing new MS therapies. In the future, it may also become possible to stimulate B cells to turn off the production of this toxic factor in people with MS.
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