MacLean Andrew J, Deimel Lachlan P, Zhou Pengcheng, ElTanbouly Mohamed A, Merkenschlager Julia, Ramos Victor, Santos Gabriela S, Hägglöf Thomas, Mayer Christian T, Hernandez Brianna, Gazumyan Anna, Nussenzweig Michel C
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, 10065, USA.
Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
bioRxiv. 2024 Nov 29:2024.11.26.625430. doi: 10.1101/2024.11.26.625430.
Increased antibody affinity over time after vaccination, known as affinity maturation, is a prototypical feature of immune responses. Recent studies have shown that a diverse collection of B cells, producing antibodies with a wide spectrum of different affinities, are selected into the plasma cell (PC) pathway. How affinity-permissive selection enables PC affinity maturation remains unknown. Here we report that PC precursors (prePC) expressing high affinity antibodies receive higher levels of T follicular helper (Tfh)-derived help and divide at higher rates than their lower affinity counterparts once they leave the GC. Thus, differential cell division by selected prePCs accounts for how diverse precursors develop into a PC compartment that mediates serological affinity maturation.
疫苗接种后抗体亲和力随时间增加，即亲和力成熟，是免疫反应的一个典型特征。最近的研究表明，多种产生具有广泛不同亲和力抗体的B细胞被选入浆细胞（PC）途径。允许亲和力的选择如何使PC亲和力成熟仍然未知。在这里，我们报告说，表达高亲和力抗体的PC前体（prePC）比离开生发中心（GC）的低亲和力对应物接受更高水平的滤泡辅助性T细胞（Tfh）衍生的帮助，并且分裂速度更快。因此，选定的prePC的差异细胞分裂解释了不同的前体如何发展成为介导血清学亲和力成熟的PC区室。
