B-cell subsets: cellular interactions and relevance in multiple sclerosis

There has been longstanding interest in how B-cell responses may contribute to the pathology of neurological diseases. Traditionally, the premise has been that any such contribution relates to the potential of B cells to produce autopathogenic antibodies. Targeting autoantibodies continues to be an important therapeutic approach, particularly in disorders where the role of antibodies is relatively well established, such as in certain inflammatory disorders of peripheral nerves or the neuromuscular junction. In other conditions, such as multiple sclerosis, the role of circulating antibodies targeting the CNS has been less clear, although pathologic studies continue to implicate CNS-reactive antibodies, as well as B cells within the CNS compartment. Recently, new insights into fundamental properties of B cells have suggested that these cells may contribute in an antibody-independent fashion, both to normal immune responses, and in the context of immune mediated diseases. Here, we will consider the potential roles of antibody-dependent as well as antibody-independent B-cell involvement in multiple sclerosis. The topic is of particular interest at a time that B-cell-directed therapies are being evaluated for this and other autoimmune diseases.