Immune Receptor Activation Laboratory, The Francis Crick Institute, London, UK.
Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, London, UK.
Nat Immunol. 2023 Aug;24(8):1281-1294. doi: 10.1038/s41590-023-01559-1. Epub 2023 Jul 13.
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.
生发中心（GCs）需要持续提供抗原，以促进针对病原体和疫苗的抗体亲和力成熟。GC B 细胞的一个主要抗原来源是滤泡树突状细胞（FDCs）上展示的免疫复合物（ICs）。在这里，我们表明 FDC 的空间组织调节 GC 中的抗原动力学。我们确定了 FDC 网络内的异质性。虽然整个亮区（LZ）FDC 网络最初捕获 ICs，但只有网络的中央细胞作为抗原储存库，来自随后免疫的不同抗原在该处共定位。从机制上讲，中央 LZ FDC 上的 CR2 膜密度比外周 LZ FDC 略高，这大大增加了 IC 保留半衰期。尽管重复免疫逐渐使中央 FDC 饱和，但 B 细胞反应仍然有效，因为新的抗原部分取代了旧的抗原。这些结果揭示了在 GC 反应过程中塑造 FDC 上抗原展示的原则。
