Pure anti-dsDNA mAbs need chromatin structures to promote glomerular mesangial deposits in BALB/c mice

Kristin Andreassen Fenton, Berit Tømmers, Tony Marion, Ole Petter Rekvig

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The glomerular targets for nephritogenic antibodies have been identified as membrane-associated chromatin fragments. The processes responsible for their deposition are poorly understood. To determine early events in antibody-mediated nephritis, we injected highly pure anti-dsDNA mAbs into BALB/c mice. Mice receiving one dose of anti-dsDNA mAbs were sacrificed 6 or 24 h later. No direct binding of mAbs to glomerular membranes or to the mesangial matrix was observed by immune electron microscopy. In contrast, repeated injections of the same antibodies over 4 weeks resulted in deposition of electron dense structures predominantly in the mesangial matrix. These structures contained mAbs and chromatin fragments as determined by co-localization immune electron microscopy. Biotinylated anti-dsDNA mAbs, injected into nephritic (NZB × NZW)F1 or MRLlpr/lpr mice were detected in newly formed electron dense structures within glomerular capillary membranes. There were no correlation between mAb affinity for DNA, as determined by surface plasmon resonance analyses, and ability to bind chromatin fragments in vivo. No direct binding of mAbs to inherent membrane antigens was observed. Quantification of DNA in sera before and after one single injection of antibodies revealed increased DNA levels at 6 h after injection of anti-dsDNA mAb, and lower levels after 24 h. Repeated injections of anti-dsDNA caused an increase in circulating DNA. These results indicate that availability of chromatin fragments, presumable in circulation, is important for glomerular mesangial matrix deposition of anti-dsDNA antibody-containing immune complexes in context of lupus nephritis.

Original languageEnglish (US)
Pages (from-to)179-188
Number of pages10
JournalAutoimmunity
Volume43
Issue number2
DOIs
StatePublished - Mar 1 2010

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Chromatin
Injections
Membranes
Antibodies
DNA
Electron Microscopy
Electrons
Lupus Nephritis
Surface Plasmon Resonance
Nephritis
Antigen-Antibody Complex
Anti-Idiotypic Antibodies
Kidney
Antigens
Serum

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Pure anti-dsDNA mAbs need chromatin structures to promote glomerular mesangial deposits in BALB/c mice. / Fenton, Kristin Andreassen; Tømmers, Berit; Marion, Tony; Rekvig, Ole Petter.

In: Autoimmunity, Vol. 43, No. 2, 01.03.2010, p. 179-188.

Research output: Contribution to journalArticle

Fenton, Kristin Andreassen ; Tømmers, Berit ; Marion, Tony ; Rekvig, Ole Petter. / Pure anti-dsDNA mAbs need chromatin structures to promote glomerular mesangial deposits in BALB/c mice. In: Autoimmunity. 2010 ; Vol. 43, No. 2. pp. 179-188.
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