Department of Internal Medicine, University of Genoa, Genoa, Italy.
PLoS One. 2012;7(2):e31903. doi: 10.1371/journal.pone.0031903. Epub 2012 Feb 15.
Systemic lupus erythematosus (SLE) is characterized by the production of a wide array of autoantibodies and dysregulation of B cell function. The leukocyte associated Immunoglobulin (Ig)-like receptor (LAIR)1 is a transmembrane molecule belonging to Ig superfamily which binds to different types of collagen. Herein, we have determined the expression and function of LAIR1 on B lymphocyte from SLE patients. LAIR1 expression in peripheral blood B lymphocytes from 54 SLE, 24 mixed connective tissue disease (MCTD), 20 systemic sclerosis (SSc) patients, 14 rheumatoid arthritis (RA) and 40 sex and age matched healthy donors (HD) have been analyzed by immunofluorescence. The effect of LAIR1 ligation by specific monoclonal antibodies, collagen or collagen producing mesenchymal stromal cells from reactive lymph nodes or bone marrow on Ig production by pokeweed mitogen and B cell receptor (BCR)-mediated NF-kB activation was assessed by ELISA and TransAM assay. The percentage of CD20(+) B lymphocytes lacking or showing reduced expression of LAIR1 was markedly increased in SLE and MCTD but not in SSc or RA patients compared to HD. The downregulation of LAIR1 expression was not dependent on corticosteroid therapy. Interestingly, LAIR1 engagement by collagen or collagen-producing mesenchymal stromal cells in SLE patients with low LAIR1 expression on B cells delivered a lower inhibiting signal on Ig production. In addition, NF-kB p65 subunit activation upon BCR and LAIR1 co-engagement was less inhibited in SLE patients than in HD. Our findings indicate defective LAIR1 expression and function in SLE B lymphocytes, possible contributing to an altered control of B lymphocytes behavior.
系统性红斑狼疮（SLE）的特征是产生广泛的自身抗体和 B 细胞功能失调。白细胞相关免疫球蛋白（Ig）样受体（LAIR）1 是一种跨膜分子，属于 Ig 超家族，可与不同类型的胶原蛋白结合。在此，我们确定了 SLE 患者 B 淋巴细胞上 LAIR1 的表达和功能。通过免疫荧光分析了 54 例 SLE、24 例混合性结缔组织病（MCTD）、20 例系统性硬化症（SSc）患者、14 例类风湿关节炎（RA）和 40 名性别和年龄匹配的健康供体（HD）外周血 B 淋巴细胞中 LAIR1 的表达。通过 ELISA 和 TransAM 测定评估了特异性单克隆抗体、胶原蛋白或反应性淋巴结或骨髓中的胶原蛋白产生间充质基质细胞对植物血凝素和 B 细胞受体（BCR）介导的 NF-κB 激活诱导的 Ig 产生的 LAIR1 结合作用。与 HD 相比，SLE 和 MCTD 患者中缺乏或表达降低的 CD20+ B 淋巴细胞的 LAIR1 百分比明显增加，但 SSc 或 RA 患者则没有。LAIR1 表达的下调不依赖于皮质类固醇治疗。有趣的是，在 LAIR1 表达较低的 SLE 患者中，胶原蛋白或胶原蛋白产生的间充质基质细胞与 LAIR1 的结合传递了较低的抑制 Ig 产生信号。此外，与 HD 相比，SLE 患者中 BCR 和 LAIR1 共结合时 NF-κB p65 亚基的激活抑制作用较弱。我们的研究结果表明，SLE B 淋巴细胞中存在缺陷的 LAIR1 表达和功能，可能导致 B 淋巴细胞行为的控制异常。
