Autoantibodies make a U-turn: the toll hypothesis for autoantibody specificity.
Like the immune response itself, our efforts to understand the "rules" for self-nonself discrimination are constantly evolving. The discovery of pattern recognition receptors-the Toll-like receptor (TLR) family in particular-shifted the emphasis of self-nonself recognition from lymphocytes functioning in the adaptive immune system to antigen-presenting cells (APCs) functioning in the innate immune system. Two new articles, one in a recent issue (1) and one in this issue (see Vollmer et al. [2] on p. 1575), demonstrate that antigen-antibody complexes containing RNAs activate B lymphocytes and dendritic cells (DCs) through interaction with TLR7 and/or TLR8. From these and other papers, one begins to see how specific types of autoantigens-by virtue of their capacity to act as TLR ligands-favor autoantibody production. This is known as the Toll hypothesis.
Martin
David A
DA
Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Elkon
Keith B
KB
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells; D006801:Humans; D012313:RNA / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D051200:Toll-Like Receptor 8 / Q000276:immunology*
D001323:Autoantibodies; C495348:TLR7 protein, human; C495349:TLR8 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D012313:RNA