The elusive role of B lymphocytes and islet autoantibodies in (human) type 1 diabetes

The role of B lymphocytes in the pathogenesis of type 1 diabetes in humans is not entirely evident. These cells are presumed to be important, but this assumption is largely based on animal models of autoimmune diabetes, where compelling evidence for the contribution of both B lymphocytes and insulin-specific autoantibodies to this disease is in place. For humans, this is much less the case; the exact way in which B lymphocytes and/or autoantibodies may contribute to type 1 diabetes is not yet known but the possibilities include a pathogenic function ('fire'), or they may represent a surrogate of loss of immune tolerance to beta cells ('smoke') or, indeed, they could be a marker of an attempt at immune regulation ('ice water'). In this issue of Diabetologia, a study by Willcox et al (DOI: 10.1007/s00125-017-4221-7) adds new information but no greater clarity on the relevance of B lymphocytes in type 1 diabetes, showing a decrease in germinal centre frequencies in donors with recent-onset type 1 diabetes compared with control donors and donors with longstanding type 1 diabetes. These new findings may guide the research community to design experiments to unambiguously define whether B lymphocytes or their products function as fire, smoke or perhaps ice water in the immunopathogenesis of type 1 diabetes.