The early activation of memory B cells from Wiskott-Aldrich syndrome patients is suppressed by CD19 downregulation
The early activation of memory B cells from Wiskott-Aldrich syndrome patients is suppressed by CD19 downregulation
复制标题
Wiskott-Aldrich 综合征患者记忆 B 细胞的早期激活受到 CD19 下调的抑制。
DOI：
10.1182/blood-2016-03-703579
复制
发表时间：
2016-09-29
期刊：
影响因子：
20.3
通讯作者：
Liu, Chaohong
中科院分区：
文献类型：
--
作者：
Bai, Xiaoming;Zhang, Yongjie;Liu, Chaohong
Wiskott-Aldrich syndrome (WAS) pediatric patients exhibit a deficiency in humoral immune memory. However, the mechanism by which Wiskott-Aldrich syndrome protein (WASP) regulates the differentiation and activation of memory B cells remains elusive. Here we examine the early activation events of memory B cells from the peripheral blood mononuclear cells of WAS patients and age-matched healthy controls (HCs) using total internal reflection fluorescence microscopy. In response to stimulation through the B-cell receptor (BCR), memory B cells from HCs showed significantly higher magnitudes of BCR clustering and cell spreading than naive B cells from the same individuals. This was associated with increases in CD19 recruitment to the BCR and the activation of its downstream signaling molecule Btk and decreases in FcγRIIB recruitment and the activation of its downstream molecule Src homology 2-containing inositol 5' phosphatase (SHIP). However, these enhanced signaling activities mediated by CD19 and Btk are blocked in memory B cells from WAS patients, whereas the activation of FcγRIIB and SHIP was increased. Although the expression levels of CD19, Btk, and FcγRIIB did not change between CD27(-) and CD27(+) B cells of HCs, the protein and mRNA levels of CD19 but not Btk and FcγRIIB were significantly reduced in both CD27(-) and CD27(+) B cells of WAS patients, compared with those of HCs. Overall, our study suggests that WASP is required for memory B-cell activation, promoting the activation by positive regulating CD19 transcription and CD19 recruitment to the BCR.
