Background/Aims Recent evidence implicates an important role for age-associated B cells (ABCs), defined as CD19+IgD-CD27-T-bet+ B cells, in healthy ageing, following viral infection and in active SLE. We know that co-receptors of the B cell receptor (BCR) such as CD19 and other activating receptors can influence B cell activation through distinct pathways. Therefore, we compared the expression of CD19 in B cell subpopulations including ABCs in ageing and SLE. Methods Peripheral blood was obtained from six young (<45 years) healthy participants, seven elderly (>65 years) healthy participants and eight patients with SLE (25-65 years). We performed flow cytometry on peripheral blood mononuclear cells to analyse the expression of extracellular and intracellular markers. We performed statistical analysis using GraphPad Prism v7. Results CD19hi B cell frequency was at least 10-fold higher in T-bet+ cells as a whole and particularly enriched in IgD-CD27-T-bet+, ABCs, in all groups, p < 0.05. The geometric mean fluorescent intensity (gMFI, expression) of CD40 was significantly lower in IgD-CD27-T-bet+ subpopulations compared to IgD-CD27-T-bet- B cell subpopulations in all groups (Table). In all groups, in CD19+T-bet+ cells, compared to CD19+T-bet- cells, there was a significantly increased frequency of IFNγR+ cells, TLR4+ cells, TLR7+ cells and TLR9+ cells (p < 0.05 for all) with remarkable difference noted in SLE patients for TLR7 and TLR9, p < 0.01 (Table). In the switched memory IgD-CD27+ and ABCs, TLR7 expression was significantly higher (p < 0.01) in SLE patients (mean 43.8% and 18.5% respectively) compared to elderly participants (mean 13.5% compared to 4.3% respectively). Conclusion High levels of expression of CD19 is a characteristic feature of ABCs and CD19hiT-bet+ cells predominantly belong to the IgD-CD27-T-bet+ ABC subpopulation. CD19hi IgD-CD27-T-bet+ cells also had significantly lower expression of CD40 and higher expression of IFNγR and TLR7 and TLR9, suggesting that CD19 plays a significant role in moderating activation of ABCs triggered through T-independent, IFNγR-TLR-T-bet pathway. Taken together with the significant role of CD19 in regulating signalling threshold of B cell activation, and its stable expression across different B cell developmental stages, these data provide compelling mechanistic rationale for targeting CD19 to deplete B cells, including potentially pathogenic age-associated, in autoimmune disease such as SLE. Disclosure K. Shah: None. V. Poon: None. S.J. Taylor: None. C. Klein: Corporate appointments; CK is employed by Roche. Shareholder/stock ownership; CK has patents and stock ownership at Roche. F. Kollert: Corporate appointments; FK is employed by Roche. Shareholder/stock ownership; FK has stock ownership at Roche. F. Schuler: Corporate appointments; FS is employed by Roche. Shareholder/stock ownership; FS has patents and stock ownership at Roche. S. Mathur: None. M. Castelino: None. D. Sen: None. J. Cambridge: None. M. Cragg: None. M. Leandro: None. A. Akbar: None. V. Reddy: None.

中文翻译：

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P160 高水平的 CD19 表达是衰老和自身免疫中与年龄相关的 B 细胞的特征

背景/目标 最近的证据表明年龄相关 B 细胞 (ABC)（定义为 CD19+IgD-CD27-T-bet+ B 细胞）在健康衰老、病毒感染后和活动性 SLE 中发挥着重要作用。我们知道 B 细胞受体 (BCR) 的共受体（例如 CD19）和其他激活受体可以通过不同的途径影响 B 细胞激活。因此，我们比较了衰老和 SLE 中 B 细胞亚群（包括 ABC）中 CD19 的表达。方法从六名年轻(＜45岁)健康参与者、七名老年(＞65岁)健康参与者和八名SLE患者(25-65岁)获得外周血。我们对外周血单个核细胞进行流式细胞术来分析细胞外和细胞内标志物的表达。我们使用 GraphPad Prism v7 进行统计分析。结果在所有组中，T-bet+细胞中CD19hi B细胞频率至少高出10倍，特别是在IgD-CD27-T-bet+、ABC中富集，p＜1。 0.05。与所有组中的 IgD-CD27-T-bet- B 细胞亚群相比，IgD-CD27-T-bet+ 亚群中 CD40 的几何平均荧光强度（gMFI，表达）均显着较低（表）。在所有组中，在CD19+T-bet+细胞中，与CD19+T-bet-细胞相比，IFNγR+细胞、TLR4+细胞、TLR7+细胞和TLR9+细胞的频率显着增加（全部p＜0.05），且显着增加。 SLE 患者中 TLR7 和 TLR9 存在差异，p < 1。 0.01（表）。在切换记忆的 IgD-CD27+ 和 ABC 中，SLE 患者的 TLR7 表达显着高于老年参与者（平均分别为 13.5% 和 4.3%）（分别为 43.8% 和 18.5%）（p < 0.01）。结论 CD19 高水平表达是 ABC 的特征，CD19hiT-bet+ 细胞主要属于 IgD-CD27-T-bet+ ABC 亚群。 CD19hi IgD-CD27-T-bet+ 细胞的 CD40 表达也显着降低，而 IFNγR、TLR7 和 TLR9 表达较高，表明 CD19 在调节由 T 不依赖的 IFNγR-TLR-T- 触发的 ABC 激活中发挥着重要作用。下注途径。结合 CD19 在调节 B 细胞激活信号阈值中的重要作用及其在不同 B 细胞发育阶段的稳定表达，这些数据为靶向 CD19 消除 B 细胞（包括潜在的致病性年龄相关）提供了令人信服的机制原理。自身免疫性疾病，如系统性红斑狼疮 (SLE)。披露 K. Shah：无。 V. 潘：没有。 SJ泰勒：没有。 C. Klein：公司任命； CK 受雇于罗氏公司。股东/股权； CK 拥有罗氏的专利和股权。 F. Kollert：公司任命； FK 受雇于罗氏公司。股东/股权； FK 拥有罗氏公司的股权。 F. Schuler：公司任命； FS 受雇于罗氏公司。股东/股权； FS 在罗氏拥有专利和股权。 S.马图尔：没有。 M。卡斯泰利诺：没有。 D.森：没有。 J.剑桥：没有。 M.克拉格：没有。 M·莱安德罗：没有。 A·阿克巴：没有。 V.雷迪：没有。