美国洛克菲勒大学Gabriel D. Victora研究组发现，预先存在的抗体和记忆性T细胞的帮助对记忆性生发中心的动态产生相反的影响。这一研究成果于2024年6月4日在线发表在国际学术期刊《免疫》上。

研究人员表示，再次接触抗原会产生大量抗体反应，并促使次级生发中心（GC）的形成。小鼠的记忆性GC几乎完全由初始B细胞组成，而记忆性抗体则绝大多数来自记忆B细胞。

研究人员揭示了细胞和血清之间的这种分工。重复免疫相同的抗原后，记忆性GC的四聚体分析表明，这些结构中的B细胞结合抗原的能力明显下降。用病毒变体蛋白增殖可恢复记忆性GC中的抗原结合，通过条件性缺失Prdm1对原代抗体分泌细胞进行基因消减也可恢复记忆性GC中的抗原结合，这表明先前存在的抗体抑制了记忆性GC的反应。

在B细胞和T细胞特异性脱钩的载体实验中，记忆性T细胞帮助检测不到抗原结合的B细胞进入GC。因此，抗体介导的反馈会引导记忆性GC B细胞远离先前的靶标表位，并实现对变异表位的特异性靶标，从而对疫苗接种方案产生影响。

附：英文原文

Title: Opposing effects of pre-existing antibody and memory T cell help on the dynamics of recall germinal centers

Author: Arin Schiepers, Marije F.L. van’t Wout, Alvaro Hobbs, Luka Mesin, Gabriel D. Victora

Issue&Volume: 2024-06-04

Abstract: Re-exposure to an antigen generates abundant antibody responses and drives the formationof secondary germinal centers (GCs). Recall GCs in mice consist almost entirely ofnave B cells, whereas recall antibodies derive overwhelmingly from memory B cells. Here,we examine this division between cellular and serum compartments. After repeated immunizationwith the same antigen, tetramer analyses of recall GCs revealed a marked decreasein the ability of B cells in these structures to bind the antigen. Boosting with viralvariant proteins restored antigen binding in recall GCs, as did genetic ablation ofprimary-derived antibody-secreting cells through conditional deletion of Prdm1, demonstrating suppression of GC recall responses by pre-existing antibodies. Inhapten-carrier experiments in which B and T cell specificities were uncoupled, memoryT cell help allowed B cells with undetectable antigen binding to access GCs. Thus,antibody-mediated feedback steers recall GC B cells away from previously targetedepitopes and enables specific targeting of variant epitopes, with implications forvaccination protocols.

DOI: 10.1016/j.immuni.2024.05.009

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00263-2