PDF(Pubmed)
Abstract：
Re-exposure to an antigen generates abundant antibody responses and drives the formation of secondary germinal centers (GCs). Recall GCs in mice consist almost entirely of naïve B cells, whereas recall antibodies derive overwhelmingly from memory B cells. Here, we examine this division between cellular and serum compartments. After repeated immunization with the same antigen, tetramer analyses of recall GCs revealed a marked decrease in the ability of B cells in these structures to bind the antigen. Boosting with viral variant proteins restored antigen binding in recall GCs, as did genetic ablation of primary-derived antibody-secreting cells through conditional deletion of Prdm1, demonstrating suppression of GC recall responses by pre-existing antibodies. In hapten-carrier experiments in which B and T cell specificities were uncoupled, memory T cell help allowed B cells with undetectable antigen binding to access GCs. Thus, antibody-mediated feedback steers recall GC B cells away from previously targeted epitopes and enables specific targeting of variant epitopes, with implications for vaccination protocols.
摘要：
再暴露于抗原会产生丰富的抗体反应，并驱动次级生发中心（GC）的形成。回想一下小鼠中的GC几乎完全由初始B细胞组成，而回忆抗体绝大多数来自记忆B细胞。这里,我们检查了细胞和血清区室之间的这种划分。用相同的抗原反复免疫后，召回GC的四聚体分析显示，这些结构中B细胞结合抗原的能力显着降低。增强病毒变异蛋白恢复了回忆GCs中的抗原结合，通过Prdm1的条件性缺失对原代衍生抗体分泌细胞进行基因切除,证明已有抗体抑制了GC回忆反应.在B和T细胞特异性分离的半抗原载体实验中，记忆T细胞帮助B细胞与检测不到的抗原结合进入GC。因此，抗体介导的反馈使GCB细胞远离先前靶向的表位，并能够特异性靶向变体表位，对疫苗接种方案有影响。
