WASp Is Crucial for the Unique Architecture of the Immunological Synapse in Germinal Center B-Cells

作者全名："Li, Yanan; Bhanja, Anshuman; Upadhyaya, Arpita; Zhao, Xiaodong; Song, Wenxia"

作者地址："[Li, Yanan; Zhao, Xiaodong] Chongqing Med Univ, Childrens Hosp, Dept Rheumatol & Immunol, Chongqing, Peoples R China; [Li, Yanan; Zhao, Xiaodong] Natl Clin Res Ctr Child Hlth & Disorders, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing Key Lab Child Infect & Immun, Minist Educ,Key Lab Child Dev & Disorders, Chongqing, Peoples R China; [Li, Yanan; Bhanja, Anshuman; Song, Wenxia] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA; [Upadhyaya, Arpita] Univ Maryland, Dept Phys, College Pk, MD 20742 USA; [Upadhyaya, Arpita] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA"

通信作者："Zhao, XD (corresponding author), Chongqing Med Univ, Childrens Hosp, Dept Rheumatol & Immunol, Chongqing, Peoples R China.; Zhao, XD (corresponding author), Natl Clin Res Ctr Child Hlth & Disorders, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing Key Lab Child Infect & Immun, Minist Educ,Key Lab Child Dev & Disorders, Chongqing, Peoples R China."

来源：FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000667211900001

JCR分区：Q1

影响因子：5.5

年份：2021

卷号：9

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：B-lymphocytes; germinal center; actin; WASp; signal transduction; immunological synapse

摘要："B-cells undergo somatic hypermutation and affinity maturation in germinal centers. Somatic hypermutated germinal center B-cells (GCBs) compete to engage with and capture antigens on follicular dendritic cells. Recent studies show that when encountering membrane antigens, GCBs generate actin-rich pod-like structures with B-cell receptor (BCR) microclusters to facilitate affinity discrimination. While deficiencies in actin regulators, including the Wiskott-Aldrich syndrome protein (WASp), cause B-cell affinity maturation defects, the mechanism by which actin regulates BCR signaling in GBCs is not fully understood. Using WASp knockout (WKO) mice that express Lifeact-GFP and live-cell total internal reflection fluorescence imaging, this study examined the role of WASp-mediated branched actin polymerization in the GCB immunological synapse. After rapid spreading on antigen-coated planar lipid bilayers, GCBs formed microclusters of phosphorylated BCRs and proximal signaling molecules at the center and the outer edge of the contact zone. The centralized signaling clusters localized at actin-rich GCB membrane protrusions. WKO reduced the centralized micro-signaling clusters by decreasing the number and stability of F-actin foci supporting GCB membrane protrusions. The actin structures that support the spreading membrane also appeared less frequently and regularly in WKO than in WT GCBs, which led to reductions in both the level and rate of GCB spreading and antigen gathering. Our results reveal essential roles for WASp in the generation and maintenance of unique structures for GCB immunological synapses."

基金机构：US National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 GM064625]; National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [8161001201]; US National Science FoundationNational Science Foundation (NSF) [PHY 1915534]

基金资助正文：This work was supported by the US National Institute of Health grant R01 GM064625 to WS. YL was supported by National Science Foundation of China grant #8161001201 to XZ. AU was supported by the US National Science Foundation grant PHY 1915534.