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PLoS One. 2012;7(8):e44131. doi: 10.1371/journal.pone.0044131. Epub 2012 Aug 29.

The largely normal response to Toll-like receptor 7 and 9 stimulation and the enhanced expression of SIGIRR by B cells in systemic lupus erythematosus.

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  • 1Department of Immunology, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing, China.

Abstract

BACKGROUND:

Altered Toll-like receptor (TLR) signaling has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). The present study was undertaken to characterize responses of B cells from SLE patients to TLR7 and TLR9 stimulation and to explore the potential role of single immunoglobulin interleukin-1 receptor related molecule (SIGIRR) in the regulation of TLR-mediated responses of SLE B cells.

METHODOLOGY/PRINCIPAL FINDINGS:

Peripheral blood mononuclear cells (PBMC) were isolated from 64 patients with SLE and 37 healthy donors. CD19+ B cells purified using microbeads were cultured with TLR7 or TLR9 agonists. Cell proliferation was measured by thymine incorporation and the frequency of antibody-secreting cells was determined by ELISPOT assay. SIGIRR expression in PBMCs and B cells was analyzed using flow cytometry analysis. In contrast to the enhanced proliferation following B cell receptor (BCR) engagement, B cells from SLE patients exhibited a virtually normal proliferative response to TLR7 or TLR9 stimulation. Moreover, B cells from SLE patients and healthy donors were almost equally competent to differentiate into antibody-secreting cells upon TLR engagement except for a reduction in the generation of IgG-secreting cells by TLR9-stimulated lupus B cells. In line with these somehow unexpected observations, SLE B cells were found to express a significantly higher level of SIGIRR than normal B cells.

CONCLUSIONS/SIGNIFICANCE:

Despite the reported upregulation of TLR7 and TLR9 expression in B cell from SLE patients, their responses to TLR stimulation were largely normal. The increased expression of the negative regulator SIGIRR may be partly responsible for the "balance of terror".

PMID:
22952899
[PubMed - indexed for MEDLINE]
PMCID:
PMC3430643
Free PMC Article
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