FIG. 1.Figure 1
Model for autoantigen presentation in B-cell–depleted NOD mice. Autoantigen presentation is normally balanced between B-cells and dendritic cells (DCs) in mice ( 16 ). A : NOD autoantigen presentation. However, B-cell cognate presentation of pancreatic autoantigens may dominate in NOD mice because B-cell selection ( 17 ) and innate cell APC function are impaired ( 18 ). As a result, B-cell–driven pathogenic CD4 + T-cell expansion and effector function leads to β-cell destruction and insulin deficiency. B : Presentation without B-cells. Mature B-cell depletion in NOD mice eliminates the initiating role of B-cells in disease pathogenesis but shifts antigen presentation to other APCs that may reduce CD4 + T-cell activation in favor of Treg induction or expansion and lead to a tolerogenic state or honeymoon period without disease. C : Following B-cell reconstitution, previously induced Tregs may limit autoreactive T-cell activation and expansion, thereby enforcing long-term tolerance