Re-establishing tolerance to DNA in humanized and murine models of SLE

Autoimmun Rev. 2010 May;9(7):499-502. doi: 10.1016/j.autrev.2010.02.009. Epub 2010 Feb 10.

Abstract

DNA-specific B cells in SLE represent a logical target for therapeutic intervention. We hypothesize that it is possible to re-establish tolerance to native DNA in SCID mice with cells transferred from SLE patients or from lupus-prone MRL/lpr mice by administering chimeric molecules, containing a monoclonal antibody against inhibitory B cell receptors coupled to a peptide that antigenically mimics DNA. These protein-engineered molecules are able to co-crosslink selectively the antigen receptors of B cells possessing anti-native DNA specificity with the inhibitory surface receptors, thus delivering a strong suppressive signal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / genetics*
  • Antibodies, Antinuclear / immunology
  • Antibodies, Bispecific / immunology
  • Antibodies, Bispecific / therapeutic use*
  • B-Lymphocytes / immunology
  • Biomimetics
  • DNA / immunology
  • Disease Models, Animal
  • Feedback, Physiological
  • Humans
  • Immune Tolerance
  • Immunotherapy* / trends
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / therapy*
  • Mice
  • Protein Engineering

Substances

  • Antibodies, Antinuclear
  • Antibodies, Bispecific
  • DNA