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.