Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.
Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.
Immunity. 2024 Jul 9;57(7):1618-1628.e4. doi: 10.1016/j.immuni.2024.05.009. Epub 2024 Jun 4.
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.
再次接触抗原会引发大量的抗体反应，并驱动次级生发中心（GC）的形成。在小鼠中，回忆 GC 几乎完全由幼稚 B 细胞组成，而回忆抗体则主要来自记忆 B 细胞。在这里，我们研究了细胞和血清区室之间的这种划分。在重复用相同抗原免疫后，通过四聚体分析发现，这些结构中 B 细胞结合抗原的能力显著下降。用病毒变异蛋白进行增强，以及通过条件性删除 Prdm1 对初级抗体分泌细胞进行遗传消融，都恢复了回忆 GC 中的抗原结合，表明预先存在的抗体抑制了 GC 的回忆反应。在半抗原-载体实验中，当 B 和 T 细胞特异性分离时，记忆 T 细胞辅助使抗原结合检测不到的 B 细胞能够进入 GC。因此，抗体介导的反馈使回忆 GC B 细胞远离以前的靶向表位，并能够针对变异表位进行特异性靶向，这对疫苗接种方案具有重要意义。
