Subjects: Biology >> Biophysics >> Biology submitted time 2016-05-15
Wan, Zhengpeng
Chen, Xiangjun
Chen, Yingjia
Wang, Jing
Cao, Yiyun
Liu, Wanli
Chen, Haodong
Wang, Fei
Tang, Zhuo
Ji, Qinghua
Lou, Jizhong
Abstract： B lymphocytes use B cell receptors (BCRs) to sense the physical features of the antigens. However, the sensitivity and threshold for the activation of BCRs resulting from the stimulation by mechanical forces are unknown. Here, we addressed this question using a double-stranded DNA-based tension gauge tether system serving as a predefined mechanical force gauge ranging from 12 to 56 pN. We observed that IgM-BCR activation is dependent on mechanical forces and exhibits a multi-threshold effect. In contrast, the activation of isotype-switched IgG- or IgE-BCR only requires a low threshold of less than 12 pN, providing an explanation for their rapid activation in response to antigen stimulation. Mechanistically, we found that the cytoplasmic tail of the IgG-BCR heavy chain is both required and sufficient to account for the low mechanical force threshold. These results defined the mechanical force sensitivity and threshold that are required to activate different isotyped BCRs.
Peer Review Status:
Awaiting Review
Subjects: Biology >> Biophysics >> Oncology submitted time 2016-05-11
Wang, Fei
Yang, Li
Gao, Qun
Huang, Lan
Zhang, Yi
Wang, Fei
Zhang, Yi
Gao, Qun
Wang, Liping
Zhang, Yi
Wang, Jing
Wang, Shengdian
Zhang, Bin
Abstract： Malignant pleural effusion (MPE) is a common complication caused by malignant diseases. However, subjectivity, poor sensitivity, and substantial false-negative rates of cytology assay hamper accurate MPE diagnosis. The aim of this study was to assess whether CD163+CD14+ tumor-associated macrophages (TAMs) could be used as a biomarker for enabling sensitive and specific MPE diagnosis. Pleural effusion samples and peripheral blood samples were collected from 50 MPE patients and 50 non-malignant pleural effusion (NMPE) patients, respectively. Flow cytometry was performed to analyze cell phenotypes, and RT-qPCR was used to detect cytokine expression in these monocytes and macrophages. A blinded validation study (n = 40) was subsequently performed to confirm the significance of CD163+CD14+ TAMs in MPE diagnosis. Student's t test, rank sum test, and receiver operating characteristic curve analysis were used for statistical analysis. Notably, CD163+CD14+ cell frequency in MPE was remarkably higher than that in NMPE (P < 0.001). In a blinded validation study, a sensitivity of 78.9 % and a specificity of 100 % were obtained with CD163+CD14+ TAMs as a MPE biomarker. In total (n = 140), by using a cutoff level of 3.65 %, CD163+CD14+ cells had a sensitivity of 81.2 % and a specificity of 100 % for MPE diagnosis. Notably, MPE diagnosis by estimating CD163+CD14+ cells in pleural effusion could be obtained one week earlier than that obtained by cytological examination. CD163+CD14+ macrophages could be potentially used as an immune diagnostic marker for MPE and has better assay sensitivity than that of cytological analysis.
Peer Review Status:Awaiting Review
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