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

• Published in: PloS one 2012-08, Vol.7 (8), p.e44131-e44131
• Main Authors: Zhu, Yun-Yan, Su, Yin, Li, Zhan-Guo, Zhang, Yu
• Format: Article
• Language: English
• Subjects: Adult; Analysis; Antigens; Autoimmune diseases; B-cell receptor; B-Lymphocytes - immunology; B-Lymphocytes - pathology; B-Lymphocytes - secretion; Biology; Case-Control Studies; CD19 antigen; Cell growth; Cell Proliferation; Chronic conditions; Cytokines; Cytometry; Demography; Deoxyribonucleic acid; Development and progression; DNA; Enzyme-linked immunosorbent assay; Female; Flow cytometry; Gene expression; Genetic aspects; Humans; Hydrocarbons; Immune system; Immunoglobulin G; Immunoglobulin G - metabolism; Immunology; Interleukin 1; Kinases; Laboratories; Leukocytes (mononuclear); Lupus; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - pathology; Lymphocytes B; Male; Medicine; Microspheres; Mortality; Nanoparticles; Pathogenesis; Patients; Peripheral blood mononuclear cells; Physiological aspects; Proteins; Receptors, Antigen, B-Cell - immunology; Receptors, Interleukin-1 - immunology; Rheumatology; Rodents; Signaling; Stimulation; Studies; Systemic lupus erythematosus; T cell receptors; Terrorism; Thymine; TLR7 protein; TLR9 protein; Toll-Like Receptor 7 - immunology; Toll-Like Receptor 9 - agonists; Toll-Like Receptor 9 - immunology; Toll-like receptors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0044131

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. 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. 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".