Nucleating autoimmunity

An IgG/DNA complex activates B cells and provokes autoimmune responses.

Tudor Toma(t.toma@ic.ac.uk)
Apr 11, 2002

Autoimmune diseases are frequently caused by abnormal production of self-antibodies but the mechanisms responsible for generating B cell autoreactivity remain unclear. In April 11 Nature, Elizabeth Leadbetter and colleagues from Boston University School of Medicine show that IgG in complex with DNA activate B cells by dual engagement of IgM and Toll-like receptors and provokes autoimmune responses (Nature 2002, 416:603-607).

Leadbetter et al. used a murine model of systemic autoimmune disease and observed that IgG2a–chromatin immune complexes mediated effective activation of autoimmune B cells. This process required the synergistic engagement of the antigen receptor and a member of theMyD88-dependent Toll-like receptor (TLR) family.

"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," said the authors.

In addition, "drugs that specifically target Toll-like receptor signaling...

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