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TY - JOUR AU - Leadbetter, Elizabeth A. AU - Rifkin, Ian R. AU - Hohlbaum, Andreas M. AU - Beaudette, Britte C. AU - Shlomchik, Mark J. AU - Marshak-Rothstein, Ann PY - 2002 DA - 2002/04/01 TI - Chromatin–IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors JO - Nature SP - 603 EP - 607 VL - 416 IS - 6881 AB - 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. SN - 1476-4687 UR - https://doi.org/10.1038/416603a DO - 10.1038/416603a ID - Leadbetter2002 ER -