Toll-like Receptor 7-Dependent Loss of B Cell Tolerance in Pathogenic Autoantibody Knockin Mice

Academic Article

Abstract

  • 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. © 2006 Elsevier Inc. All rights reserved.
  • Published In

  • Immunity  Journal
  • Digital Object Identifier (doi)

    Author List

  • Berland R; Fernandez L; Kari E; Han JH; Lomakin I; Akira S; Wortis HH; Kearney JF; Ucci AA; Imanishi-Kari T
  • Start Page

  • 429
  • End Page

  • 440
  • Volume

  • 25
  • Issue

  • 3