Bourke Emer, Bosisio Daniela, Golay Josee, Polentarutti Nadia, Mantovani Alberto
Department of Immunology and Cell Biology, Mario Negri Institute, Milan, Italy.
Blood. 2003 Aug 1;102(3):956-63. doi: 10.1182/blood-2002-11-3355. Epub 2003 Apr 10.
The present study was designed to investigate the expression of members of the toll-like receptor (TLR) family in human B cells. High-density, resting, and low-density activated tonsillar B cells expressed TLR9 and TLR10 mRNA transcripts at the highest levels. Expression was higher in activated B cells than in resting cells. Analysis of a range of resting and activated human leukocyte populations revealed that mRNA expression of TLR10 was restricted to B cells. Stimulation of resting B cells with anti-mu and anti-CD40 antibodies or with Staphylococcus aureus Cowan I bacteria (SAC) increased expression of TLR9 and TLR10. TLR1 and TLR4 expression were not significantly induced by B-cell activation. Interestingly, a CpG oligonucleotide, a TLR9 agonist, also stimulated TLR9 expression in B cells. Exposure to anti-mu antibodies augmented TLR9 expression, concomitantly and dramatically increasing the responsiveness of B cells to CpG oligonucleotides in terms of proliferation and chemokine (CC chemokine ligand 3 [CCL3] and CCL22) production. Epstein-Barr virus (EBV)-transformed cell lines and other cell lines representative of mature B-cell neoplasias (Burkitt lymphoma, follicular lymphoma, multiple myeloma) expressed TLR9 and/or TLR10, whereas pre-B cell lines were negative. These results show that normal and neoplastic human B lymphocytes express a distinct TLR repertoire including TLR9 and TLR10 and that expression is increased upon engagement of the antigen receptor complex or TLR9 itself. Regulated expression of selected TLRs in B cells is likely to play an important role in linking innate and adaptive immune responses in normal and pathologic conditions.
本研究旨在调查Toll样受体（TLR）家族成员在人B细胞中的表达。高密度、静止和低密度活化的扁桃体B细胞中，TLR9和TLR10 mRNA转录本表达水平最高。活化B细胞中的表达高于静止细胞。对一系列静止和活化的人类白细胞群体分析显示，TLR10的mRNA表达仅限于B细胞。用抗μ和抗CD40抗体或金黄色葡萄球菌Cowan I菌（SAC）刺激静止B细胞可增加TLR9和TLR10的表达。B细胞活化未显著诱导TLR1和TLR4的表达。有趣的是，一种TLR9激动剂CpG寡核苷酸也可刺激B细胞中TLR9的表达。暴露于抗μ抗体可增强TLR9的表达，同时显著提高B细胞对CpG寡核苷酸在增殖和趋化因子（CC趋化因子配体3 [CCL3]和CCL22）产生方面的反应性。爱泼斯坦-巴尔病毒（EBV）转化的细胞系以及代表成熟B细胞肿瘤（伯基特淋巴瘤、滤泡性淋巴瘤、多发性骨髓瘤）的其他细胞系表达TLR9和/或TLR10，而前B细胞系为阴性。这些结果表明，正常和肿瘤性人B淋巴细胞表达包括TLR9和TLR10在内的独特TLR谱，并且在抗原受体复合物或TLR9自身激活后表达增加。B细胞中特定TLR的调节表达可能在正常和病理条件下连接固有免疫和适应性免疫反应中发挥重要作用。
