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".
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".