球三糖神经酰胺
生发中心
免疫
生物
病毒学
免疫系统
免疫学
B细胞
医学
抗体
病理
疾病
法布里病
作者
Pankaj Sharma,Xiaolong Zhang,Kevin Ly,Yuxiang Zhang,Yu Hu,Adam Yongxin Ye,Jiannan Hu,Ji Hyung Kim,Min Lou,Chong Wang,Quinton Celuzza,Yuji Kondo,Koichi Furukawa,David R. Bundle,Koichi Furukawa,Frederick W. Alt,Florian Winau
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2024-02-16
卷期号:383 (6684)
标识
DOI:10.1126/science.adg0564
摘要
Influenza viruses escape immunity owing to rapid antigenic evolution, which requires vaccination strategies that allow for broadly protective antibody responses. We found that the lipid globotriaosylceramide (Gb3) expressed on germinal center (GC) B cells is essential for the production of high-affinity antibodies. Mechanistically, Gb3 bound and disengaged CD19 from its chaperone CD81, permitting CD19 to translocate to the B cell receptor complex to trigger signaling. Moreover, Gb3 regulated major histocompatibility complex class II expression to increase diversity of T follicular helper and GC B cells reactive with subdominant epitopes. In influenza infection, elevating Gb3, either endogenously or exogenously, promoted broadly reactive antibody responses and cross-protection. These data demonstrate that Gb3 determines the affinity and breadth of B cell immunity and has potential as a vaccine adjuvant.
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