CLINTEC, Karolinska Institutet, SE-14157 Stockholm, Sweden.
J Leukoc Biol. 2011 Feb;89(2):177-87. doi: 10.1189/jlb.0210061. Epub 2010 Sep 15.
NLRs are recently discovered PRRs detecting substructures of peptidoglycans and triggering innate immunity. NLRs are expressed in several cell types, but the presence in human B lymphocytes is still unknown. This study aimed to investigate expression and function of NLRs in human B lymphocytes. B cells were isolated and analyzed for mRNA and protein expression. The functional responsiveness of NOD1 and NOD2 was investigated upon stimulation with the cognate ligands, with or without stimulation via IgM/IgD/CD40 and/or selected TLR agonists. A differential expression of NLRs was demonstrated in blood-derived and tonsillar B cells, whereas no variations were found among naive, germinal center, or memory B cells. Stimulation with the ligands alone did not induce B cell activation. However, upon concomitant BCR triggering, an increase in proliferation was seen, together with an induction of cell surface markers (CD27, CD69, CD71, CD80, CD86, and CD95) and prolonged survival. Peripheral B cells were activated by NOD1 and NOD2 ligands, whereas tonsil-derived B cells responded solely to NOD1. In contrast, costimulation with CD40L failed to induce activation. Additionally, it was found that NLR ligands could enhance TLR-induced proliferation of B cells. The present study demonstrates expression of functional NLRs in human B cells. We show that NOD1 and NOD2 have the ability to augment the BCR-induced activation independently of physical T cell help. Hence, NLRs represent a new pathway for B cell activation and a potentially important host defense system against bacterial infections.
NLRs 是最近发现的识别肽聚糖亚结构并触发先天免疫的 PRRs。NLRs 在多种细胞类型中表达，但在人类 B 淋巴细胞中的存在仍不清楚。本研究旨在研究 NLRs 在人类 B 淋巴细胞中的表达和功能。分离 B 细胞并分析其 mRNA 和蛋白表达。在 IgM/IgD/CD40 和/或选定的 TLR 激动剂刺激下，研究了 NOD1 和 NOD2 的功能反应性及其与配体的相互作用。在血液来源的和扁桃体来源的 B 细胞中显示出 NLRs 的差异表达，而在幼稚、生发中心或记忆 B 细胞中没有发现差异。单独刺激配体不会诱导 B 细胞激活。然而，在同时 BCR 触发下，观察到增殖增加，同时诱导细胞表面标志物（CD27、CD69、CD71、CD80、CD86 和 CD95）和延长存活。外周 B 细胞被 NOD1 和 NOD2 配体激活，而扁桃体来源的 B 细胞仅对 NOD1 有反应。相反，CD40L 的共刺激未能诱导激活。此外，还发现 NLR 配体可以增强 TLR 诱导的 B 细胞增殖。本研究证明了功能性 NLRs 在人类 B 细胞中的表达。我们表明，NOD1 和 NOD2 具有独立于物理 T 细胞辅助增强 BCR 诱导激活的能力。因此，NLRs 代表了 B 细胞激活的新途径，是对抗细菌感染的潜在重要宿主防御系统。
