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Semin Immunol. 2011 Apr;23(2):106-12. doi: 10.1016/j.smim.2011.01.016.

Toll-like receptor driven B cell activation in the induction of systemic autoimmunity.

Author information

1
Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA. nmgreen@bu.edu

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.

PMID:
21306913
PMCID:
PMC3070769
DOI:
10.1016/j.smim.2011.01.016
[Indexed for MEDLINE]
Free PMC Article

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