Type 1 Diabetes (T1D) is characterized by the gradual loss of insulin-producing beta cells, which are eliminated by autoreactive cells infiltrating the pancreas. In humans and mouse models of the disease, T1D susceptibility is determined by genetic factors and is greatly influenced by environmental triggers (1). Progression to T1D is usually preceded by a period of anti-islet autoantibody production, which often can last for years (2). Today, autoantibodies are most widely used as serum biomarker (3), but T-cell readouts and metabolome studies are underway as they may strengthen diagnosis, prognosis and most importantly bring forward effective protocols for prevention and cure. T follicular helper (TFH) cells are essential for the formation of germinal centers (GCs), specialized structures in secondary lymphoid organs where maturation of B cells into high-affinity plasma cells and long-lived memory B cells takes place. It has become clear that precise control of the GC response is important for the production of optimal antibody responses that are devoid of selfreactivity. The exact mechanism by which autoreactive B cells are eliminated during this process is not fully understood, however the number of TFH cells together with a specialized subset to FOXP3+ regulatory T cells, namely T follicular regulatory cells (TFR), finely control the survival of pathogen-specific high-affinity B cells. It is currently not known whether TFH or TFR cells are involved in the production of islet-reactive, autoantibody-producing B cells in patients with T1D. However, given that autoantibodies emerge prior to disease onset, the effect of TFH cells in T1D progression can be inferred. With this study we aim at identifying whether TFH and TFR cells are implicated in autoantibody development in T1D. Investigating this mechanism poses a cardinal opportunity to increase the pipeline of therapeutic targets and to improve the number of disease biomarkers.