Evaluating the role of B cells in autoimmune disease: more than just initiators of disease?

Autoantibodies are a common feature of all autoimmune diseases. The molecules against which autoantibodies are produced dictate which organ/s are targeted during autoimmune attack and help to define disease pathogenesis and presentation. Although autoantibody production is seen as a key feature of autoimmune disease onset, not every individual with autoantibodies goes on to develop autoimmune disease, suggesting that other factors are also at play. A series of shared genetic susceptibility loci common to many autoimmune diseases have been detected, including the HLA class I and class II molecules, CTLA-4 and PTPN22. These genes encode products that play a key role in presenting antigen to and controlling activation of T cells. These observations have helped to support the theory that for many autoimmune diseases B cells may play a role in producing autoantibodies and initiating disease onset, whereas T cells play a more active role in disease progression. As a consequence, less focus has been placed on investigating whether disrupted B cell signalling/autoantibody production/clearance could also be playing a role in autoimmune disease susceptibility. Due to advances in our understanding of the human genome and the development of new genetic analysis techniques, association of several genes and by inference several molecules involved in controlling B cell activation and autoreactivity are starting to be identified. Combined with increases in our understanding of T cell independent B cell activity, including bacterial/viral activation of B cells and the ability of B cells to influence other immune cells, advances are providing additional evidence of how B cells could be playing an active role in autoimmunity above and beyond autoantibody production. There is, therefore, a growing body of thought to suggest that disrupted B cell activation and/or autoantibody production/clearance could be playing a key role in most autoimmune diseases and that greater understanding of these pathways could be used to develop improved therapeutic interventions