Dysregulation of germinal centres in autoimmune disease

In germinal centres, somatic hypermutation and B cell selection increase antibody affinity and specificity for the immunizing antigen, but the generation of autoreactive B cells is an inevitable by-product of this process. Here, we review the evidence that aberrant selection of these autoreactive B cells can arise from abnormalities in each of the germinal centre cellular constituents-B cells, T follicular helper cells, follicular dendritic cells and tingible body macrophages-or in the supply of antigen. As the progeny of germinal centre B cells includes long-lived plasma cells, selection of autoreactive B cells can propagate long-lived autoantibody responses and cause autoimmune diseases. Elucidation of crucial molecular signals in germinal centres has led to the identification of novel therapeutic targets.