+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

RAGE-independent autoreactive B cell activation in response to chromatin and HMGB1/DNA immune complexes

RAGE-independent autoreactive B cell activation in response to chromatin and HMGB1/DNA immune complexes

Autoimmunity 43(1): 103-110

Increasing evidence suggests that the excessive accumulation of apoptotic or necrotic cellular debris may contribute to the pathology of systemic autoimmune disease. HMGB1 is a nuclear DNA-associated protein, which can be released from dying cells thereby triggering inflammatory processes. We have previously shown that IgG2a-reactive B cell receptor (BCR) transgenic AM14 B cells proliferate in response to endogenous chromatin immune complexes (ICs), in the form of the anti-nucleosome antibody PL2-3 and cell debris, in a TLR9-dependent manner, and that these ICs contain HMGB1. Activation of AM14 B cells by these chromatin ICs was inhibited by a soluble form of the HMGB1 receptor, RAGE-Fc, suggesting HMGB1-RAGE interaction was important for this response. To further explore the role of HMGB1 in autoreactive B cell activation, we assessed the capacity of purified calf thymus HMGB1 to bind dsDNA fragments and found that HMGB1 bound both CG-rich and CG-poor DNA. However, HMGB1-DNA complexes could not activate AM14 B cells unless HMGB1 was bound by IgG2a and thereby able to engage the BCR. To ascertain the role of RAGE in autoreactive B cell responses to chromatin ICs, we intercrossed AM14 and RAGE-deficient mice. We found that spontaneous and defined DNA ICs activated RAGE+ and RAGE(- ) AM14 B cells to a comparable extent. These results suggest that HMGB1 promotes B cell responses to endogenous TLR9 ligands through a RAGE-independent mechanism.

(PDF emailed within 0-6 h: $19.90)

Accession: 055333027

Download citation: RISBibTeXText

PMID: 20014975

DOI: 10.3109/08916930903384591

Related references

HMGB1 modulates Lewis cell autophagy and promotes cell survival via RAGE-HMGB1-Erk1/2 positive feedback during nutrient depletion. Immunobiology 220(5): 539-544, 2016

The activation of HMGB1 as a progression factor on inflammation response in normal human bronchial epithelial cells through RAGE/JNK/NF-κB pathway. Molecular and Cellular Biochemistry 380(1-2): 249-257, 2014

Receptor for advanced glycation end products (RAGE) partially mediates HMGB1-ERKs activation in clear cell renal cell carcinoma. Journal of Cancer Research and Clinical Oncology 138(1): 11-22, 2012

Toll-like receptor 9-dependent and -independent dendritic cell activation by chromatin-immunoglobulin G complexes. Journal of Experimental Medicine 199(12): 1631-1640, 2004

Antibody-independent activation of C1. I. Differences in the mechanism of C1 activation by nonimmune activators and by immune complexes: C1r-independent activation of C1s by cardiolipin vesicles. Journal of Immunology 138(6): 1864-1870, 1987

Comparison of CpG s-ODNs, chromatin immune complexes, and dsDNA fragment immune complexes in the TLR9-dependent activation of rheumatoid factor B cells. Journal of Endotoxin Research 10(4): 247-251, 2004

Autophagy-mediated HMGB1 release promotes gastric cancer cell survival via RAGE activation of extracellular signal-regulated kinases 1/2. Oncology Reports 33(4): 1630-1638, 2016

Immunogenic cell death biomarkers HMGB1, RAGE, and DNAse indicate response to radioembolization therapy and prognosis in colorectal cancer patients. International Journal of Cancer 132(10): 2349-2358, 2013

Relationship of soluble RAGE and RAGE ligands HMGB1 and EN-RAGE to endothelial dysfunction in type 1 and type 2 diabetes mellitus. Experimental and Clinical Endocrinology & Diabetes 120(5): 277-281, 2013

B-cell activation by T-cell-independent type 2 antigens as an integral part of the humoral immune response to pathogenic microorganisms. Immunological Reviews 176: 154-170, 2000

The activation of autoreactive T cell induced by immunization with fusions of dendritic cell and hepatoma cell is not enough to make the immune mediated liver injury. Hepatology 34(4 Pt 2): 530A, October, 2001

Activation of Toll-like receptor, RAGE and HMGB1 signalling in malformations of cortical development. Brain 134(Pt 4): 1015-1032, 2011

HMGB1-DNA complex-induced autophagy limits AIM2 inflammasome activation through RAGE. Biochemical and Biophysical Research Communications 450(1): 851-856, 2014

Cell death in the pathogenesis of immune-mediated diseases: the role of HMGB1 and DAMP-PAMP complexes. Swiss Medical Weekly 141: W13256-W13256, 2011

Hmgb1 promotes wound healing of 3T3 mouse fibroblasts via RAGE-dependent ERK1/2 activation. Cell Biochemistry and Biophysics 57(1): 9-17, 2010