HMGB1 is an endogenous immune adjuvant released by necrotic cells

Abstract

Immune responses against pathogens require that microbial components promote the activation of antigen‐presenting cells (APCs). Autoimmune diseases and graft rejections occur in the absence of pathogens; in these conditions, endogenous molecules, the so‐called ‘innate adjuvants’, activate APCs. Necrotic cells contain and release innate adjuvants; necrotic cells also release high‐mobility group B1 protein (HMGB1), an abundant and conserved constituent of vertebrate nuclei. Here, we show that necrotic HMGB1−/− cells have a reduced ability to activate APCs, and HMGB1 blockade reduces the activation induced by necrotic wild‐type cell supernatants. In vivo , HMGB1 enhances the primary antibody responses to soluble antigens and transforms poorly immunogenic apoptotic lymphoma cells into efficient vaccines.