Toll-like receptor-dependent immune complex activation of B cells and dendritic cells

Melissa B. Uccellini, Ana M. Avalos, Ann Marshak-Rothstein, Gregory A. Viglianti

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

9 Scopus citations

Abstract

High titers of autoantibodies reactive with DNA/RNA molecular complexes are characteristic of autoimmune disorders such as systemic lupus erythematosus (SLE). In vitro and in vivo studies have implicated Toll-like receptor 9 (TLR9) and Toll-like receptor 7 (TLR7) in the activation of the corresponding autoantibody producing B cells. Importantly, TLR9/TLR7-deficiency results in the inability of autoreactive B cells to proliferate in response to DNA/RNA-associated autoantigens in vitro, and in marked changes in the autoantibody repertoire of autoimmune-prone mice. Uptake of DNA/RNA-associated autoantigen immune complexes (ICs) also leads to activation of dendritic cells (DCs) through TLR9 and TLR7. The initial studies from our lab involved ICs formed by a mixture of autoantibodies and cell debris released from dying cells in culture. To better understand the nature of the mammalian ligands that can effectively activate TLR7 and TLR9, we have developed a methodology for preparing ICs containing defined DNA fragments that recapitulate the immunostimulatory activity of the previous "black box" ICs. These reagents reveal an important role for nucleic acid sequence, even when the ligand is mammalian DNA.

Original languageEnglish
Title of host publicationToll-Like Receptors
Subtitle of host publicationMethods and Protocols
EditorsClaire McCoy, Luke O'Neill
Pages363-380
Number of pages18
DOIs
StatePublished - 2009
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume517
ISSN (Print)1064-3745

Keywords

  • AM14 transgenic BCR
  • Autoantibodies
  • B cells
  • Biotinylated DNA
  • Endogenous ligands
  • Flt3L-DCs
  • IFNα
  • Immune complex
  • Rheumatoid factor B cell
  • TLR7
  • TLR9

Fingerprint

Dive into the research topics of 'Toll-like receptor-dependent immune complex activation of B cells and dendritic cells'. Together they form a unique fingerprint.

Cite this