Antibody affinity maturation occurs in the germinal center (GC), a highly dynamic structure that arises upon antigen stimulation and recedes after infection is resolved. While the magnitude of the GC reaction is highly fluctuating and depends on antigens or pathological conditions, it is unclear whether GCs are assembled ad hoc in different locations or in preexisting niches within B cell follicles. We show that follicular dendritic cells (FDCs), the essential cellular components of the GC architecture, form a predetermined number of clusters. The total number of FDC clusters is the same on several different genetic backgrounds and is not altered by immunization or inflammatory conditions. In unimmunized and germ-free mice, a few FDC clusters contain GC B cells; in contrast, immunization or autoimmune milieu significantly increases the frequency of FDC clusters occupied by GC B cells. Excessive occupancy of GC niches by GC B cells after repeated immunizations or in autoimmune conditions suppresses subsequent antibody responses to new antigens. These data indicate that the magnitude of the GC reaction is restricted by a fixed number of permissive GC niches containing preassembled FDC clusters. This finding may help in the future design of vaccination strategies and in the modulation of antibody-mediated autoimmunity.

抗体亲和力成熟发生在生发中心 (GC)，这是一种高度动态的结构，在抗原刺激时出现，并在感染解决后消退。虽然 GC 反应的幅度波动很大并且取决于抗原或病理条件，但尚不清楚 GC 是在不同位置临时组装还是在 B 细胞滤泡内预先存在的壁龛中组装。我们表明滤泡树突状细胞 (FDC) 是 GC 结构的基本细胞成分，形成预定数量的簇。FDC 簇的总数在几种不同的遗传背景下是相同的，并且不会因免疫或炎症条件而改变。在未免疫和无菌小鼠中，少数 FDC 簇包含 GC B 细胞；相比之下，免疫或自身免疫环境显着增加了被 GC B 细胞占据的 FDC 簇的频率。GC B 细胞在重复免疫后或在自身免疫条件下过度占据 GC 生态位会抑制随后的抗体对新抗原的反应。这些数据表明 GC 反应的幅度受到包含预组装 FDC 簇的固定数量的允许 GC 壁龛的限制。这一发现可能有助于未来疫苗接种策略的设计和抗体介导的自身免疫的调节。这些数据表明 GC 反应的幅度受到包含预组装 FDC 簇的固定数量的允许 GC 壁龛的限制。这一发现可能有助于未来疫苗接种策略的设计和抗体介导的自身免疫的调节。这些数据表明 GC 反应的幅度受到包含预组装 FDC 簇的固定数量的允许 GC 壁龛的限制。这一发现可能有助于未来疫苗接种策略的设计和抗体介导的自身免疫的调节。