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EMBO Rep. 2004 Aug;5(8):825-30. Epub 2004 Jul 23.

HMGB1 is an endogenous immune adjuvant released by necrotic cells.

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  • 1Cancer Immunotherapy & Gene Therapy Program, Clinical Immunology Unit H San Raffaele Scientific Institute and Vita-Salute San Raffaele University, DIBIT 3A1, Chromatin Dynamics Unit, Via Olgettina 58, 20132 Milano, Italy.


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.

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