Department of Laboratory Medicine, Yale University, New Haven, Connecticut, USA.
Nat Immunol. 2010 Jun;11(6):535-42. doi: 10.1038/ni.1877. Epub 2010 May 9.
Memory B and plasma cells (PCs) are generated in the germinal center (GC). Because follicular helper T cells (T(FH) cells) have high expression of the immunoinhibitory receptor PD-1, we investigated the role of PD-1 signaling in the humoral response. We found that the PD-1 ligands PD-L1 and PD-L2 were upregulated on GC B cells. Mice deficient in PD-L2 (Pdcd1lg2(-/-)), PD-L1 and PD-L2 (Cd274(-/-)Pdcd1lg2(-/-)) or PD-1 (Pdcd1(-/-)) had fewer long-lived PCs. The mechanism involved more GC cell death and less T(FH) cell cytokine production in the absence of PD-1; the effect was selective, as remaining PCs had greater affinity for antigen. PD-1 expression on T cells and PD-L2 expression on B cells controlled T(FH) cell and PC numbers. Thus, PD-1 regulates selection and survival in the GC, affecting the quantity and quality of long-lived PCs.
记忆 B 细胞和浆细胞（PCs）在生发中心（GC）中生成。由于滤泡辅助 T 细胞（T(FH)细胞）高表达免疫抑制受体 PD-1，我们研究了 PD-1 信号在体液反应中的作用。我们发现 GC B 细胞上 PD-1 配体 PD-L1 和 PD-L2 上调。PD-L2（Pdcd1lg2(-/-)）、PD-L1 和 PD-L2（Cd274(-/-)Pdcd1lg2(-/-)）或 PD-1（Pdcd1(-/-)）缺失的小鼠中，长寿 PC 较少。其机制涉及在没有 PD-1 的情况下，GC 细胞死亡增加和 T(FH)细胞细胞因子产生减少；这种影响是选择性的，因为剩余的 PC 对抗原具有更高的亲和力。T 细胞上的 PD-1 表达和 B 细胞上的 PD-L2 表达控制 T(FH)细胞和 PC 数量。因此，PD-1 调节 GC 中的选择和存活，影响长寿 PC 的数量和质量。
