title: Toll-like receptor driven B cell activation in the induction of systemic autoimmunity.
abstract: Studies over the past decade have demonstrated a key role for pattern recognition receptors in the activation of autoreactive B cells. Self reactive B cells that manage to escape negative selection often express relatively low affinity receptors for self antigens (ignorant B cells), and can only be activated by integrating a relatively weak BCR signal with signals from additional receptors. Members of the toll-like receptor (TLR) gene family, and especially the nucleic acid binding receptors TLR 7, 8 and 9, appear to play a key role in this regard and promote the production of autoantibodies reactive with DNA- or RNA-associated autoantigens. These autoantibodies are able to form immune complexes with soluble or cell-bound ligands, and these immune complexes can in turn activate a second round of proinflammatory cells that further contribute to the autoimmune disease process. Recent data have emerged showing a pathogenic role for TLR7, with an opposing, protective role for TLR9. Targeting these disregulated pathways offers a therapeutic opportunity to treat autoimmune diseases without crippling the entire immune system. Further understanding of the role of specific receptors, cell subsets, and inhibitory signals that govern these TLR-associated pathways will enable future therapeutics to be tailored to specific categories of autoimmune disease.
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA. nmgreen@bu.edu
authors.forename: Nathaniel M
authors.initials: NM
authors.lastname: Green
authors.forename: Ann
authors.initials: A
authors.lastname: Marshak-Rothstein
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology; D008213:Lymphocyte Activation; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007370:Interferon Type I; D051193:Toll-Like Receptors