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T 细胞与 B 细胞在生发中心形成过程中的相互作用:一个三步模型。

T cell interactions with B cells during germinal center formation, a three-step model.

机构信息

Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.

出版信息

Immunol Rev. 2019 Mar;288(1):37-48. doi: 10.1111/imr.12737.

Abstract

Establishment of effective immunity against invading microbes depends on continuous generation of antibodies that facilitate pathogen clearance. Long-lived plasma cells with the capacity to produce high affinity antibodies evolve in germinal centers (GCs), where B cells undergo somatic hypermutation and are subjected to affinity-based selection. Here, we focus on the cellular interactions that take place early in the antibody immune response during GC colonization. Clones bearing B-cell receptors with different affinities and specificities compete for entry to the GC, at the boundary between the B-cell and T-cell zones in lymphoid organs. During this process, B cells compete for interactions with T follicular helper cells, which provide selection signals required for differentiation into GC cells and antibody secreting cells. These cellular engagements are long-lasting and depend on activation of adhesion molecules that support persistent interactions and promote transmission of signals between the cells. Here, we discuss how interactions between cognate T and B cells are primarily maintained by three types of molecular interactions: homophilic signaling lymphocytic activation molecule (SLAM) interactions, T-cell receptor: peptide-loaded major histocompatibility class II (pMHCII), and LFA-1:ICAMs. These essential components support a three-step process that controls clonal selection for entry into the antibody affinity maturation response in the GC, and establishment of long-lasting antibody-mediated immunity.

摘要

建立有效抵御入侵微生物的免疫力取决于持续产生有助于清除病原体的抗体。在生发中心 (GC) 中,能够产生高亲和力抗体的长寿浆细胞进化,B 细胞经历体细胞超突变并受到亲和力选择。在这里,我们重点关注在 GC 定植过程中抗体免疫反应早期发生的细胞相互作用。带有不同亲和力和特异性的 B 细胞受体的克隆竞争进入 GC,GC 位于淋巴器官的 B 细胞和 T 细胞区之间的边界处。在此过程中,B 细胞竞争与滤泡辅助 T 细胞的相互作用,滤泡辅助 T 细胞提供分化为 GC 细胞和抗体分泌细胞所需的选择信号。这些细胞相互作用是持久的,取决于支持持续相互作用和促进细胞间信号传递的粘附分子的激活。在这里,我们讨论了同源 T 和 B 细胞之间的相互作用如何主要通过三种类型的分子相互作用来维持:同种型信号淋巴细胞激活分子 (SLAM) 相互作用、T 细胞受体:加载肽的主要组织相容性复合体 II (pMHCII) 和 LFA-1:ICAMs。这些必需的组成部分支持控制克隆选择进入 GC 中的抗体亲和力成熟反应以及建立持久的抗体介导免疫的三步过程。

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