Possible Clue to Progression of MS

B cell lymphocytes, a type of immune cell, in people with multiple sclerosis (MS) may play a role in the disease's progression

Wayne State University School of Medicine researchers, working with colleagues in Canada, have found that one or more substances produced by B cell lymphocytes seem to damage the cells of the myelin sheath protecting nerves. The finding could lead to new targeted therapies for MS treatment.

B cells are a subset of lymphocytes (circulating white blood cells) that mature to become plasma cells and produce immunoglobulins - proteins that serve as antibodies. Robert Lisak, M.D., professor of neurology at Wayne State and lead author of the study says B cells also appear to have other functions, including helping to regulate other lymphocytes, particularly T cells, helping to maintain normal immune function.

In patients with MS, B cells appear to attack the brain
and spinal cord, possibly because substances
produced by the nervous system and the meninges
— the covering of the brain and spinal cord —
attract B cells.

Once within the meninges (central nervous system), the activated B cells secrete one or more substances that damage oligodendrocytes, the cells producing myelin (a protective nerve covering), says Lisak.

B cells appear to be more active in patients with MS, which may explain why they produce these toxic substances in abundance.

The brain, for the most part, can be divided into gray and white areas. Neurons are in the gray areas, while the white areas are the axons — white because oligodendrocytes make myelin, a cholesterol-rich membrane that coats the axons.

Myelin's function is to insulate the axons, akin to the plastic coating on an electrical cable. In addition, the myelin speeds communication along axons and makes all communication more reliable. When the myelin coating is attacked and degraded, impulses — messages from the brain to other parts of the body — can "leak" and be derailed from their target. Oligodendrocytes also seem to engage in other activities important to nerve cells and their axons.

The researchers isolated B cells from the blood of seven patients with relapsing-remitting MS. After growing the cells in culture medium, they collected the substances produced by the cells and injected it into the brain cells of mouse models. The scientists found significantly more oligodendrocytes from the MS group died when exposed to material produced by the B cells from the healthy control group. The team also found differences in other brain cells that interact with oligodendrocytes in the brain.

The researchers isolated B cells from the blood of seven patients with relapsing-remitting MS, and also from four healthy patients. They grew the cells in medium, then filtered the medium for substances produced by the B cells. After adding the substances produced by the B cells to the brain cells of animal models, the scientists found significantly more oligodendrocytes from the MS group died when compared to material produced by the B cells from the healthy control group.

The team also found differences in other brain cells that interact with oligodendrocytes.

Lisak: "We think this is a very significant finding, particularly for the damage to the cerebral cortex seen in patients with MS, because those areas seem to be damaged by material spreading into the brain from the meninges, which are rich in B cells adjacent to the areas of brain damage."

The team is now applying for grants from several sources to conduct further studies to identify the toxic factor or factors produced by B cells responsible for killing oligodendrocytes. Identification of the substance could lead to new therapeutic methods that could switch off the oligodendrocyte-killing capabilities of B cells, which, in turn, would help protect myelin from attacks.

The study, "Secretory products of multiple sclerosis B cells are cytotoxic to oligodendroglia in vitro," was published in the May 2012 edition of the Journal of Neuroimmunology and was recently featured in a National Multiple Sclerosis Society bulletin.

Other WSU researchers involved in the study include Joyce Benjamins, Ph.D., professor and associate chair of neurology; Samia Ragheba, Ph.D., assistant professor of neurology and immunology & microbiology; Liljana Nedelkoskaa, research assistant in neurology; and Jennifer Barger, research assistant in neurology; as well as researchers at the Montreal Neurological Institute and McGill University in Montreal. The research was supported by a National Multiple Sclerosis Society Collaborative MS Research Center Award, the Canadian Institutes of Health Research and the Multiple Sclerosis Society of Canada.

Wayne State University is one of the nation's pre-eminent public research institutions in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world. For more information about research at Wayne State University, visit http://www.research.wayne.edu

Original article: http://www.eurekalert.org/pub_releases/2012-07/wsu--wsr073112.php