IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v416y2002i6881d10.1038_416603a.html
   My bibliography  Save this article

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

Author

Listed:
  • Elizabeth A. Leadbetter

    (Boston University School of Medicine)

  • Ian R. Rifkin

    (Boston University School of Medicine)

  • Andreas M. Hohlbaum

    (Boston University School of Medicine)

  • Britte C. Beaudette

    (Boston University School of Medicine)

  • Mark J. Shlomchik

    (Yale University School of Medicine)

  • Ann Marshak-Rothstein

    (Boston University School of Medicine)

Abstract

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-γ (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.

Suggested Citation

  • Elizabeth A. Leadbetter & Ian R. Rifkin & Andreas M. Hohlbaum & Britte C. Beaudette & Mark J. Shlomchik & Ann Marshak-Rothstein, 2002. "Chromatin–IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors," Nature, Nature, vol. 416(6881), pages 603-607, April.
    • Handle: RePEc:nat:nature:v:416:y:2002:i:6881:d:10.1038_416603a
    DOI: 10.1038/416603a
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/416603a
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/416603a?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Chao Yang & Mahesh Bachu & Yong Du & Caroline Brauner & Ruoxi Yuan & Marie Dominique Ah Kioon & Giancarlo Chesi & Franck J. Barrat & Lionel B. Ivashkiv, 2022. "CXCL4 synergizes with TLR8 for TBK1-IRF5 activation, epigenomic remodeling and inflammatory response in human monocytes," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:416:y:2002:i:6881:d:10.1038_416603a. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.