英国弗朗西斯·克里克研究所Pavel Tolar研究组的研究表明，抗原在生发中心（GC）的长期驻留受控于滤泡状树突细胞（FDC）网络的空间构成。相关论文于2023年7月13日发表在《自然—免疫学》杂志上。

研究人员发现FDC空间组织调控GC中抗原的动力学。研究确定了FDC网络内的异质性。虽然整个光区（LZ）FDC网络最初捕获IC，但只有网络中央细胞充当了抗原库，与后续免疫的不同抗原共定位。从机制上讲，中央LZ FDCs中CR2膜密度的表达略高于外周LZ FDC，这大大增加了IC保留半衰期。即使重复免疫会导致中央FDC逐渐饱和，但B细胞反应仍然有效，因为新抗原部分取代了旧抗原。这些结果揭示了GC反应过程中抗原在FDC展示的机制。

据悉，生发中心需要持续可用的抗原以促进针对病原体和疫苗亲和力抗体的成熟。GC B细胞抗原主要是由滤泡树突状细胞上的免疫复合物（IC）刺激产生。

附：英文原文

Title: Long-term retention of antigens in germinal centers is controlled by the spatial organization of the follicular dendritic cell network

Author: Martnez-Riao, Ana, Wang, Shenshen, Boeing, Stefan, Minoughan, Sophie, Casal, Antonio, Spillane, Katelyn M., Ludewig, Burkhard, Tolar, Pavel

Issue&Volume: 2023-07-13

Abstract: Germinal centers (GCs) require sustained availability of antigens to promote antibody affinity maturation against pathogens and vaccines. A key source of antigens for GC B cells are immune complexes (ICs) displayed on follicular dendritic cells (FDCs). Here we show that FDC spatial organization regulates antigen dynamics in the GC. We identify heterogeneity within the FDC network. While the entire light zone (LZ) FDC network captures ICs initially, only the central cells of the network function as the antigen reservoir, where different antigens arriving from subsequent immunizations colocalize. Mechanistically, central LZ FDCs constitutively express subtly higher CR2 membrane densities than peripheral LZ FDCs, which strongly increases the IC retention half-life. Even though repeated immunizations gradually saturate central FDCs, B cell responses remain efficient because new antigens partially displace old ones. These results reveal the principles shaping antigen display on FDCs during the GC reaction.

DOI: 10.1038/s41590-023-01559-1

Source: https://www.nature.com/articles/s41590-023-01559-1