Nodality, South San Francisco, CA 94080, USA.
J Transl Med. 2012 Jun 6;10:113. doi: 10.1186/1479-5876-10-113.
Single-cell network profiling (SCNP) is a multi-parametric flow cytometry-based approach that simultaneously measures basal and modulated intracellular signaling activity in multiple cell subpopulations. Previously, SCNP analysis of a broad panel of immune signaling pathways in cell subsets within PBMCs from 60 healthy donors identified a race-associated difference in B cell anti-IgD-induced PI3K pathway activity.
The present study extended this analysis to a broader range of signaling pathway components downstream of the B cell receptor (BCR) in European Americans and African Americans using a subset of donors from the previously analyzed cohort of 60 healthy donors. Seven BCR signaling nodes (a node is defined as a paired modulator and intracellular readout) were measured at multiple time points by SCNP in PBMCs from 10 healthy donors [5 African Americans (36-51 yrs), 5 European Americans (36-56 yrs), all males].
Analysis of BCR signaling activity in European American and African American PBMC samples revealed that, compared to the European American donors, B cells from African Americans had lower anti-IgD induced phosphorylation of multiple BCR pathway components, including the membrane proximal proteins Syk and SFK as well as proteins in the PI3K pathway (S6 and Akt), the MAPK pathways (Erk and p38), and the NF-κB pathway (NF-κB). In addition to differences in the magnitude of anti-IgD-induced pathway activation, racial differences in BCR signaling kinetic profiles were observed. Further, the frequency of IgD+ B cells differed by race and strongly correlated with BCR pathway activation. Thus, the race-related difference in BCR pathway activation appears to be attributable at least in part to a race-associated difference in IgD+ B cell frequencies.
SCNP analysis enabled the identification of statistically significant race-associated differences in BCR pathway activation within PBMC samples from healthy donors. Understanding race-associated contrasts in immune cell signaling responses may be one critical component for elucidation of differences in immune-mediated disease prevalence and treatment responses.
单细胞网络分析（SCNP）是一种基于多参数流式细胞术的方法，可同时测量多个细胞亚群中基础和调节的细胞内信号活性。先前，对来自 60 名健康供体的 PBMC 中细胞亚群的广泛免疫信号通路的 SCNP 分析表明，B 细胞抗 IgD 诱导的 PI3K 途径活性存在种族相关性差异。
本研究使用先前分析的 60 名健康供体队列中的供体子集，将这种分析扩展到欧洲裔美国人和非裔美国人中 B 细胞受体（BCR）下游更广泛的信号通路成分。通过 SCNP 在 10 名健康供体（5 名非裔美国人（36-51 岁），5 名欧洲裔美国人（36-56 岁），均为男性）的 PBMC 中，在多个时间点测量了 7 个 BCR 信号节点（节点定义为配对调节剂和细胞内读出物）。
对欧洲裔美国人和非裔美国人 PBMC 样本中 BCR 信号活性的分析表明，与欧洲裔美国人供体相比，非裔美国人的 B 细胞中，包括膜近端蛋白 Syk 和 SFK 以及 PI3K 途径（S6 和 Akt）、MAPK 途径（Erk 和 p38）和 NF-κB 途径（NF-κB）在内的多个 BCR 途径成分的抗 IgD 诱导磷酸化水平较低。除了抗 IgD 诱导的途径激活幅度的差异外，还观察到 BCR 信号动力学特征的种族差异。此外，BCR 途径激活的频率因种族而异，并且与 BCR 途径激活强烈相关。因此，BCR 途径激活的种族相关性差异似乎至少部分归因于 IgD+B 细胞频率的种族相关性差异。
SCNP 分析能够确定来自健康供体的 PBMC 样本中 BCR 途径激活的具有统计学意义的种族相关性差异。了解免疫细胞信号反应中的种族相关性对比可能是阐明免疫介导疾病患病率和治疗反应差异的一个关键组成部分。
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