The Role of B Lymphocytes in Type 1 Diabetes

While autoreactive T cells are known to induce β-cell death in type 1 diabetes (T1D), self-reactive B cells also play an important role in the pathogenesis of T1D. Studies have shown that individuals living with T1D have an increased frequency of self-reactive B cells that escape from the bone marrow and populate peripheral organs, become activated, and participate in disease. These failed tolerance mechanisms may be attributed to genetic risk alleles that are associated with the development of T1D. Once in the periphery, these self-reactive B cells act as important antigen-presenting cells to autoreactive T cells and produce autoantibodies that are used to predict individuals at risk for or diagnosed with T1D. Here, we discuss the evidence that B cells are important in the pathogenesis of T1D, how these cells escape normal tolerance mechanisms, their role in disease progression, and how targeting these cells and/or monitoring them as biomarkers for response to therapy will be of clinical benefit.