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Review
. 2010 Jan:1183:58-68.
doi: 10.1111/j.1749-6632.2009.05123.x.

Innate pathways to B-cell activation and tolerance

Steve P Crampton  1 , Elisaveta Voynova, Silvia Bolland
Affiliations
Review

Innate pathways to B-cell activation and tolerance

Steve P Crampton et al. Ann N Y Acad Sci. 2010 Jan.

Abstract

B cells represent an important link between the adaptive and innate immune systems as they express both antigen-specific B-cell receptors (BCRs) as well as various Toll-like receptors (TLRs). Several checkpoints in B-cell development ensure that self-specific cells are eliminated from the mature B-cell repertoire to avoid harmful autoreactive responses. These checkpoints are controlled by BCR-mediated events but are also influenced by TLR-dependent signals from the innate immune system. Additionally, B-cell-intrinsic and extrinsic TLR signaling are critical for inflammatory events required for the clearance of microbial infections. Factors secreted by TLR-activated macrophages or dendritic cells directly influence the fate of protective and autoreactive B cells. Additionally, naive and memory B cells respond differentially to TLR ligands, as do different B-cell subsets. We review here recent literature describing intrinsic and extrinsic effects of TLR stimulation on the fate of B cells, with particular attention to autoimmune diseases.

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Figures

Figure 1
Figure 1. Innate pathways to B cell activation and tolerance
Intrinsic TLR signaling in naïve and memory B cells can lead to IgM and IgG-secreting plasma cell formation through IRAK and MyD88. Memory B cells express increased levels of TLRs and have a greater capacity to differentiate into plasma cells via TLR stimulation than naïve B cells. TLR-activated B cells can suppress T cell responses indirectly through an IL10-dependent mechanism. Type one IFN production from macrophages and dendritic cells stimulated with immune complexes or TLR agonists can promote the differentiation of B cells into plasma cells. TLR-stimulated dendritic cells and macrophages can suppress autoreactive B cell differentiation into plasma cells through IL6 and sCD40L, respectively. BAFF, produced by APCs, can also influence B cell homeostasis and differentiation into plasma cells. MyD88, UNC-93B and IRAK4 each decrease the level of autoreactive B cells in the periphery.
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