Toll is a Coreceptor

Science's STKE  16 Apr 2002:
Vol. 2002, Issue 128, pp. tw139
DOI: 10.1126/stke.2002.128.tw139

Autoimmune diseases result from inappropriate activation of B cells by self-antigens. One of these antigens is chromatin, which is recognized by imunnoglobulin G2a (IgG2a). Leadbetter et al. studied B cell proliferation in cells from a mouse model for rheumatoid arthritis and systemic lupus erythematosus. The stimulation of proliferation of these B cells by DNA antigens required the B cell receptor and the Toll-receptor adapter MyD88. In the presence of agents that impair lysosome and endosome acidification, the cellular response to the Toll receptor TLR9 is impaired. The B cells failed to respond to DNA antigens in the presence of chloroquine, an agent that impairs acidification, thus implicating the TLR9 receptor in the activation of B cells by DNA-based autoantigens. The implications of these results for autoimmune disease are discussed by Vinuesa and Goodnow.

E. A. Leadbetter, I. R. Rifkin, A. M. Hohlbaum, B. C. Beaudette, M. J. Schlomchik, A. Marshak-Rothstein, Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature 416, 603-607 (2002). [Online Journal]

C. G. Vinuesa, C. C. Goodnow, DNA drives autoimmunity. Nature 416, 595-598 (2002). [Online Journal]