Access

Article

Nature 416, 603-607 (11 April 2002) | doi:10.1038/416603a; Received 20 November 2001; Accepted 18 February 2002

Open Innovation Challenges

  • Methods to Analyze Consumer Emotions

    • Deadline: Jan 17 2010
    • Reward: $10,000 USD

    The Seeker is looking for methods to analyze consumer emotions. This Challenge requires only a writ...

  • Single-cell Analysis Platform

    • Deadline: Dec 02 2009
    • Reward: $5,000 USD

    This Challenge is looking for novel approaches to analyzing changes at a single-cell level. This is...

naturejobs

More science jobs
Post a job for free

Chromatin–IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors

Elizabeth A. Leadbetter1, Ian R. Rifkin2, Andreas M. Hohlbaum1, Britte C. Beaudette1, Mark J. Shlomchik3 & Ann Marshak-Rothstein1

  1. Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
  2. Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
  3. Departments of Laboratory Medicine and Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA

Correspondence to: Correspondence and requests for materials should be addressed to A.M.-R. (e-mail: Email: amrothst@bu.edu).

Top

Autoreactive B cells are present in the lymphoid tissues of healthy individuals, but typically remain quiescent. When this homeostasis is perturbed, the formation of self-reactive antibodies can have serious pathological consequences. B cells expressing an antigen receptor specific for self-immunoglobulin-gamma (IgG) make a class of autoantibodies known as rheumatoid factor (RF). Here we show that effective activation of RF+ B cells is mediated by IgG2a–chromatin immune complexes and requires the synergistic engagement of the antigen receptor and a member of the MyD88-dependent Toll-like receptor (TLR) family. Inhibitor studies implicate TLR9. These data establish a critical link between the innate and adaptive immune systems in the development of systemic autoimmune disease and explain the preponderance of autoantibodies reactive with nucleic acid–protein particles. The unique features of this dual-engagement pathway should facilitate the development of therapies that specifically target autoreactive B cells.

  1. Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
  2. Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
  3. Departments of Laboratory Medicine and Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA

Correspondence to: Correspondence and requests for materials should be addressed to A.M.-R. (e-mail: Email: amrothst@bu.edu).