In order to mount high-affinity antibody responses, B cells internalise specific antigens and process them into peptides loaded onto MHCII for presentation to T helper cells (TH cells). While the biochemical principles of antigen processing and MHCII loading have been well dissected, how the endosomal vesicle system is wired to enable these specific functions remains much less studied. Here, we performed a systematic microscopy-based analysis of antigen trafficking in B cells to reveal its route to the MHCII peptide-loading compartment (MIIC). Surprisingly, we detected fast targeting of internalised antigen into peripheral acidic compartments that possessed the hallmarks of the MIIC and also showed degradative capacity. In these vesicles, internalised antigen converged rapidly with membrane-derived MHCII and partially overlapped with cathepsin-S and H2-M, both required for peptide loading. These early compartments appeared heterogenous and atypical as they contained a mixture of both early and late endosomal markers, indicating a specialized endosomal route. Together, our data suggest that, in addition to in the previously reported perinuclear late endosomal MIICs, antigen processing and peptide loading could have already started in these specialized early peripheral acidic vesicles (eMIIC) to support fast peptide-MHCII presentation.

中文翻译：

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B细胞迅速将抗原和表面来源的MHCII靶向到外周降解区室中。

为了引发高亲和力的抗体反应，B细胞将特定抗原内在化并将其加工成负载在MHCII上的肽，以呈递给T辅助细胞（TH细胞）。尽管抗原加工和MHCII装载的生化原理已得到很好的剖析，但如何连接内体囊泡系统以实现这些特定功能仍需研究得多。在这里，我们对B细胞中的抗原运输进行了基于显微镜的系统分析，以揭示其通向MHCII肽装载区室（MIIC）的途径。出人意料的是，我们检测到内化抗原快速靶向具有MIIC标志并显示出降解能力的外周酸性区室。在这些囊泡中 内源性抗原与膜衍生的MHCII迅速融合，并与组织蛋白酶S和H2-M部分重叠，这两者都是肽加载所必需的。这些早期区室看起来是异质且非典型的，因为它们包含早期和晚期内体标记物的混合物，表明有专门的内体途径。总之，我们的数据表明，除了先前报道的核周内核内晚期MIICs之外，这些特殊的早期外周酸性囊泡（eMIIC）中的抗原加工和肽负载可能已经开始，以支持快速的肽-MHCII呈递。