B Cells from MS Patients Secrete Substances Toxic to Myelin Sheath Producing Cells

B-cells from patients with multiple sclerosis (MS) produce and secrete one or more substances that are toxic for brain oligodenrocytes, the type of glial cell that forms and supports the myelin sheath around axons in the central nervous system.

In contrast to the Schwann cell, which is responsible for myelination in peripheral neurons for a single axon, one oligodendrocyte is involved in the myelination of several axons in the brain.

Multiple sclerosis (MS) is an inflammatory disease in which the myelin sheaths around the axons of the brain and spinal cord are damaged by autoimmune attack, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. B cells are important in the pathogenesis of MS and some of the effects are not dependent on maturation of B cells into immunoglobulin (Ig) producing plasmablasts and plasma cells. B cells present antigens, activate T cells, and are involved in immunoregulation and cytokine secretion.

To determine if B cells from MS patients secrete products that have deleterious effects on glial cells not mediated by Ig, and to compare effects with secretory products of normal controls (NC), investigators at Wayne State University (Detroit, MI, USA; www.wayne.edu) isolated B cells from seven patients with relapsing remitting MS (RRMS) and four NCs. Supernatants were harvested and incubated with mixed central nervous system (CNS) neonatal rat glial cells.

Results published in the May 2012 issue of the Journal of Neuroimmunology revealed that supernatants from unstimulated NC B cells induced on average death of 7% of differentiated oligodendrocytes (OL); in contrast, supernatants from unstimulated B cells from RRMS patients induced death of 57% of OL.

Supernatants of stimulated B cells from NC did not increase the minimal OL death whereas stimulation of B cells from RRMS had variable results compared to unstimulated B cells. OL death did not correlate with levels of tumor necrosis factor alpha (TNF-alpha), lymphotoxin alpha (LT-alpha), interleukin 6 (IL-6), IL-10, transforming growth factor beta 1 (TGF-beta 1) or any combination or ratio of these cytokines. Analysis of 26 supernatants from NC and RRMS patients failed to detect IgM. There were very low levels of IgG in eight of the 26 supernatants, and no correlation between OL death and presence or absence of IgG.

While this study demonstrated that B cells from patients with RRMS but not NC secreted one or more factors toxic to OL, the identity of the toxic factor(s) remains unknown.

"B cells," said first author Dr. Robert Lisak, professor of neurology at Wayne State University, "are a subset of lymphocytes (a type of circulating white blood cell) that mature to become plasma cells and produce immunoglobulins, proteins that serve as antibodies. The B cells appear to have other functions, including helping to regulate other lymphocytes, particularly T cells, and helping maintain normal immune function when healthy."

"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," said Dr. Lisak.

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