HMGB1 is an endogenous immune adjuvant released by necrotic cells.
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.
Cancer 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.
Patrizia
P
Rovere-Querini
Annalisa
A
Capobianco
Paola
P
Scaffidi
Barbara
B
Valentinis
Federica
F
Catalanotti
Marta
M
Giazzon
Ingrid E
IE
Dumitriu
Susanne
S
Müller
Matteo
M
Iannacone
Catia
C
Traversari
Marco E
ME
Bianchi
Angelo A
AA
Manfredi
D000276:Adjuvants, Immunologic; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D024243:HMGB1 Protein / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D024243:HMGB1 Protein