Centro de Biologia Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
EMBO Rep. 2018 Sep;19(9). doi: 10.15252/embr.201846016. Epub 2018 Jul 9.
Successful vaccines rely on activating a functional humoral response that results from promoting a proper germinal center (GC) reaction. Key in this process is the activation of follicular B cells that need to acquire antigens and to present them to cognate CD4 T cells. Here, we report that follicular B cells can phagocytose large antigen-coated particles, a process thought to be exclusive of specialized antigen-presenting cells such as macrophages and dendritic cells. We show that antigen phagocytosis by B cells is BCR-driven and mechanistically dependent on the GTPase RhoG. Using mice, we show that phagocytosis of antigen by B cells is important for the development of a strong GC response and the generation of high-affinity class-switched antibodies. Importantly, we show that the potentiation effect of alum, a common vaccine adjuvant, requires direct phagocytosis of alum-antigen complexes by B cells. These data suggest a new avenue for vaccination approaches by aiming to deliver 1-3 μm size antigen particles to follicular B cells.
成功的疫苗依赖于激活体液免疫反应,这是通过促进适当的生发中心(GC)反应实现的。这个过程的关键是滤泡 B 细胞的激活,滤泡 B 细胞需要获取抗原并将其呈递给同源 CD4 T 细胞。在这里,我们报告滤泡 B 细胞可以吞噬大的抗原包被颗粒,这一过程被认为是专门的抗原呈递细胞(如巨噬细胞和树突状细胞)所特有的。我们表明,B 细胞对抗原的吞噬作用是由 BCR 驱动的,并且在机制上依赖于 GTPase RhoG。使用 小鼠,我们表明 B 细胞对抗原的吞噬作用对于强烈的 GC 反应的发展和高亲和力的类别转换抗体的产生是重要的。重要的是,我们表明,明矾(一种常见的疫苗佐剂)的增强作用需要 B 细胞直接吞噬明矾-抗原复合物。这些数据为疫苗接种方法提供了一个新的途径,旨在将 1-3 μm 大小的抗原颗粒递送到滤泡 B 细胞。