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.
Original language | English |
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Pages (from-to) | 825-30 |
Number of pages | 6 |
Journal | EMBO Reports |
Volume | 5 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 2004 |
Keywords
- Adjuvants, Immunologic
- Animals
- Antigens, CD/immunology
- Cell Line
- Dendritic Cells/immunology
- Fibroblasts/cytology
- HMGB1 Protein/genetics
- Humans
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Necrosis