MS was considered a white matter disease, but more recent studies have shown that grey matter can also

be seriously affected. MS is thought to be an autoimmune disorder, in which the immune cells enter the CNS and attack the myelin sheath covering the neurones, causing demyelination and, eventually, axonal damage. Demyelination leads to a variety of sensory and motor symptoms, such as optic neuritis, numbness, fatigue, spasticity, muscle weakness and cognitive impairment [2]. An autoimmune basis is supported by the mouse model experimental autoimmune encephalomyelitis (EAE), evoked by immunization with myelin antigens (e.g. spinal cord homogenate) in Freund’s adjuvant. EAE is a T cell-driven X-396 disease. Work on the resulting MS-like disease in the mouse model has suggested novel potential pathogenetic pathways and therapeutic agents, but these could not always be translated to the human disease [3]. The pleiotropic function of B cells (Fig. 1) and their potential involvement in MS pathogenesis has been overshadowed by the emphasis on T cell research in the last decade. However, recent exciting results with B cell-depleting agents highlight the pathogenetic roles for key players other than T cells. MS research is complicated by the inaccessibility of its target organ during life. Much of

the work, therefore, has Nivolumab order focused on post-mortem brains. It has been helped by the typical mixture of old and new white matter lesions in affected MS brains. Peripheral B and T cells are numerous in white matter lesions, being frequent in acute lesions and the active margins of chronic active lesions, rather than in inactive lesions [4–7]. The characteristic inflammatory infiltrates of B, T, dendritic and plasma cells are primarily perivascular [8–11]; Cediranib (AZD2171) however, CD8+ T cells, in particular, tend to invade into the surrounding parenchyma. T helper type 1 (Th1) and CD4+ and CD8+ T cells expressing interleukin (IL)-17 are found in perivascular areas [6,12]. CD4+ cells were found mainly in perivascular spaces and the meninges, where B cells were also detected [5,8,13–15]. Much information has come from analysing cerebrospinal fluid (CSF); it occupies the subarachnoid

space just outside the pia mater that tightly ensheathes the brain and spinal cord and lines the ventricles. During life, tapping CSF is the most practical way of sampling the CNS milieu. In MS patients, there is evidence of persistent intrathecal B and plasma cell activation [16,17]. The characteristic oligoclonal immunoglobulin bands (OCBs) are defined as two or more independent immunoglobulin (Ig)G bands in the electrophoretic gamma region in CSF but not serum. They are found in most patients with MS and imply an immune-mediated pathology, possibly of infectious nature. However, OCBs are also present in other inflammatory diseases of the CNS, e.g. subacute sclerosing panencephalitis, where they are directed against measles virus [18].