title: 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.
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.
  
  
  RESULTS
  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
  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".
authors.affiliation: Department of Immunology, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing, China.
authors.forename: Yun-Yan
authors.initials: YY
authors.lastname: Zhu
authors.forename: Yin
authors.initials: Y
authors.lastname: Su
authors.forename: Zhan-Guo
authors.initials: ZG
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D003710:Demography; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008297:Male; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell; D017472:Receptors, Interleukin-1; C546891:SIGIRR protein, human; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9