Toll-like receptor 7-dependent loss of B cell tolerance in pathogenic autoantibody knockin mice

Immunity. 2006 Sep;25(3):429-40. doi: 10.1016/j.immuni.2006.07.014.


Systemic lupus erythematosus (SLE) is characterized by the production of autoantibodies that are frequently directed against nucleic acid-associated antigens. To better understand how B cells reactive with such antigens are regulated, we generated a model system in which heavy and light chain genes encoding 564 immunoglobulin have been targeted to the heavy and light chain loci of the nonautoimmune C57BL/6 mouse strain. This antibody recognizes RNA, single-stranded DNA, and nucleosomes. We show that B cells expressing this immunoglobulin were activated, producing class-switched autoantibody in vivo despite the apparently normal induction of anergy. This autoantibody production was largely dependent on Toll-like receptor 7 (TLR7). We further show that production of these autoantibodies was sufficient to cause kidney pathology in these mice. These results demonstrate that the particular threat of nucleic acid-containing autoantigens lies in their ability to bind both antigen receptor and TLR7.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / biosynthesis*
  • Autoantibodies / physiology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Female
  • Humans
  • Immune Tolerance* / genetics
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / pathology
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Toll-Like Receptor 7 / deficiency
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / physiology*


  • Autoantibodies
  • Membrane Glycoproteins
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7