Heesters Balthasar A, Carroll Michael C
Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Cell Rep. 2016 Sep 20;16(12):3130-3137. doi: 10.1016/j.celrep.2016.08.049.
Affinity-mature B cells require cognate antigen, retained by follicular dendritic cells (FDCs), for clonal selection within germinal centers. Studies on how FDCs in lymphoid tissues acquire antigen have relied primarily on model protein antigens. To examine delivery of intact bacteria to FDCs, we used inactivated Streptococcus pneumonia (SP). We found that both medullary macrophages and a subset of SIGN-R1-positive dendritic cells (DCs) in the lymph node capture SP from the draining afferent lymphatics. The presence of DCs is required for initial complement activation, opsonization of the bacteria, and efficient transport of SP to FDCs. Moreover, we observed a major role for transport of bacteria to FDCs by naive B cells via a CD21-dependent pathway. We propose a mechanism by which efficient transport of SP to FDCs is dependent on DCs for initial binding and activation of complement and either direct transport to FDCs or transfer to naive B cells.
亲和力成熟的B细胞需要由滤泡树突状细胞(FDC)保留的同源抗原,以便在生发中心进行克隆选择。关于淋巴组织中的FDC如何获取抗原的研究主要依赖于模型蛋白抗原。为了研究完整细菌向FDC的递呈,我们使用了灭活的肺炎链球菌(SP)。我们发现,淋巴结中的髓质巨噬细胞和一部分SIGN-R1阳性树突状细胞(DC)从引流的输入淋巴管捕获SP。DC的存在对于初始补体激活、细菌的调理作用以及SP向FDC的有效转运是必需的。此外,我们观察到幼稚B细胞通过CD21依赖性途径将细菌转运至FDC发挥了主要作用。我们提出了一种机制,即SP向FDC的有效转运依赖于DC进行初始补体结合和激活,以及直接转运至FDC或转移至幼稚B细胞。