Activating systemic autoimmunity: B's, T's, and tolls.
A recent advance in the treatment and understanding of autoimmune disease has been the efficacy of B-cell-targeted therapy. Such therapies are effective for several such diseases, with systemic autoimmunity being a prototypical example. The mechanism of action is not fully defined, but blocking B cell Ag presentation to T cells is likely to be important. T-B interactions probably engender a positive feedback loop that amplifies and sustains autoimmunity. But how is self-tolerance first broken to initiate this loop? I propose, based on recent data, a model in which autoreactive B cells are activated first, independent of T cells, but dependent upon BCR and TLR signals. These activated B cells then break T cell tolerance, resulting in full-blown autoimmunity.
Shlomchik
Mark J
MJ
Yale University School of Medicine, Department of Laboratory Medicine, Box 208035, New Haven, CT 06520, USA. mark.shlomchik@yale.edu
D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*
D051193:Toll-Like Receptors