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生发中心输出具有高亲和性和低亲和性抗体的克隆多样性浆细胞群体。

Germinal centers output clonally diverse plasma cell populations expressing high- and low-affinity antibodies.

机构信息

MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.

Computational Biology Research Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.

出版信息

Cell. 2023 Dec 7;186(25):5486-5499.e13. doi: 10.1016/j.cell.2023.10.022. Epub 2023 Nov 10.

Abstract

Germinal centers (GCs) form in lymph nodes after immunization or infection to facilitate antibody affinity maturation and memory and plasma cell (PC) development. PC differentiation is thought to involve stringent selection for GC B cells expressing the highest-affinity antigen receptors, but how this plays out during complex polyclonal responses is unclear. We combine temporal lineage tracing with antibody characterization to gain a snapshot of PCs developing during influenza infection. GCs co-mature B cell clones with antibody affinities spanning multiple orders of magnitude; however, each generates PCs with similar efficiencies, including weak binders. Within lineages, PC selection is not restricted to variants with the highest-affinity antibodies. Differentiation is commonly associated with proliferative expansion to produce "nodes" of identical PCs. Immunization-induced GCs generate fewer PCs but still of low- and high-antibody affinities. We propose that generating low-affinity antibody PCs reflects an evolutionary compromise to facilitate diverse serum antibody responses.

摘要

生发中心(GCs)在免疫接种或感染后形成于淋巴结中,以促进抗体亲和力成熟以及记忆 B 细胞和浆细胞(PC)的发育。PC 的分化被认为涉及对表达最高亲和力抗原受体的 GC B 细胞的严格选择,但在复杂的多克隆反应中,这种情况是如何发生的尚不清楚。我们结合时间谱系追踪和抗体特征分析,获得了流感感染过程中 PC 发育的快照。GC 使具有跨越多个数量级的抗体亲和力的 B 细胞克隆共同成熟;然而,每个克隆都以相似的效率产生 PC,包括弱结合者。在谱系内,PC 的选择并不局限于具有最高亲和力抗体的变体。分化通常与增殖扩展有关,以产生相同 PC 的“节点”。免疫接种诱导的 GCs 产生的 PC 较少,但仍具有低和高抗体亲和力。我们提出,产生低亲和力抗体 PC 反映了一种进化上的妥协,以促进多样化的血清抗体反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b53/7617393/110eb1440c37/EMS203264-f001.jpg

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