B cell autonomous TLR signaling and autoimmunity - PubMed (original) (raw)

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B cell autonomous TLR signaling and autoimmunity

Almut Meyer-Bahlburg et al. Autoimmun Rev. 2008 Feb.

Abstract

B cells play a central role in the pathogenesis of multiple autoimmune diseases and the recognition of the importance of B cells in these disorders has grown dramatically in association with the remarkable success of B cell depletion as a treatment for autoimmunity. The precise mechanisms that promote alterations in B cell tolerance remain incompletely defined. There is increasing evidence, however, that TLRs play a major role in these events. Stimulation of B cells via the TLR pathway not only leads to an increase in antibody production but also promotes additional changes including cytokine production and up-regulation of activation markers increasing the effectiveness of B cells as APCs. Understanding the role of TLRs in systemic autoimmunity will not only provide insight into the disease pathogenesis but may also lead to the development of novel therapies. This article gives an overview of TLR signaling in B cells and the possible involvement of such signals in autoimmune diseases.

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Combined stimulation through the TLR and an autoreactive BCR leads to activation of B cells in multiple ways. Autoreactive B cells can then proliferate, or up-regulate co-stimulatory molecules turning them into more efficient APCs. They also secrete cytokines and can differentiate into plasma cells that produce large amounts of immunoglobulins (Ig). In addition, expression of activation induced cytidine deaminase (AID) is directly induced by TLR signals. This results in class switching to higher affinity immunoglobulins, and -if autoreactivity is retained-, increasingly pathogenic antibodies are generated.

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