From Antibody Repertoires to Cell-Cell Interactions to Molecular Networks: Bridging Scales in the Germinal Center.
From Antibody Repertoires to Cell-Cell Interactions to Molecular Networks: Bridging Scales in the Germinal Center.
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DOI：
10.3389/fimmu.2022.898078
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发表时间：
2022
影响因子：
7.3
通讯作者：
Hoffmann, Alexander
中科院分区：
文献类型：
--
作者：
Vaidehi Narayanan, Haripriya;Hoffmann, Alexander
关键词：
抗体介导的适应性免疫必须在不同年龄、遗传和免疫史的人群中提供有效的长期保护，以最小的不良反应对抗快速突变的病原体。为了掌握和利用抗体反应的复杂性，我们提倡对多尺度生发中心（GC）反应的机制性理解-前体B细胞进化高亲和力抗原特异性抗体的过程，形成血浆和记忆细胞的效应库长达数十年的保护。GC内B细胞的调节动力学是复杂的，并且在多个相互作用的空间和时间尺度上展开。在生物体规模上，在数周至数年内，由各种B细胞克隆谱系形成的抗体序列库随时间调节抗体的数量和质量。在组织和细胞尺度上，在数小时至数周内，B细胞通过与局部基质、抗原和辅助T细胞的空间分布相互作用经历选择。在分子尺度上，在数秒到数天内，细胞内信号传导、转录和表观遗传网络调节B细胞命运并塑造其克隆谱系。我们总结了我们目前对这些尺度的理解，并确定了连接它们的缺失环节。我们认为，B细胞和GC反应动力学的定量多尺度数学模型提供了预测框架，可以将基本的免疫学知识应用于合理的疫苗设计等实际挑战。
Antibody-mediated adaptive immunity must provide effective long-term protection with minimal adverse effects, against rapidly mutating pathogens, in a human population with diverse ages, genetics, and immune histories. In order to grasp and leverage the complexities of the antibody response, we advocate for a mechanistic understanding of the multiscale germinal center (GC) reaction – the process by which precursor B-cells evolve high-affinity antigen-specific antibodies, forming an effector repertoire of plasma and memory cells for decades-long protection. The regulatory dynamics of B-cells within the GC are complex, and unfold across multiple interacting spatial and temporal scales. At the organism scale, over weeks to years, the antibody sequence repertoire formed by various B-cell clonal lineages modulates antibody quantity and quality over time. At the tissue and cellular scale, over hours to weeks, B-cells undergo selection via spatially distributed interactions with local stroma, antigen, and helper T-cells. At the molecular scale, over seconds to days, intracellular signaling, transcriptional, and epigenetic networks modulate B-cell fates and shape their clonal lineages. We summarize our current understanding within each of these scales, and identify missing links in connecting them. We suggest that quantitative multi-scale mathematical models of B-cell and GC reaction dynamics provide predictive frameworks that can apply basic immunological knowledge to practical challenges such as rational vaccine design.
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DOI：
10.1126/science.aac4919
发表时间：
2015-08-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gitlin AD;Mayer CT;Oliveira TY;Shulman Z;Jones MJ;Koren A;Nussenzweig MC
通讯作者：
Nussenzweig MC
淋巴细胞昼夜节律的时钟控制淋巴结运输和适应性免疫反应。
影响因子：
32.4
作者：
Druzd D;Matveeva O;Ince L;Harrison U;He W;Schmal C;Herzel H;Tsang AH;Kawakami N;Leliavski A;Uhl O;Yao L;Sander LE;Chen CS;Kraus K;de Juan A;Hergenhan SM;Ehlers M;Koletzko B;Haas R;Solbach W;Oster H;Scheiermann C
通讯作者：
Scheiermann C
影响因子：
8.8
作者：
Almaden JV;Tsui R;Liu YC;Birnbaum H;Shokhirev MN;Ngo KA;Davis-Turak JC;Otero D;Basak S;Rickert RC;Hoffmann A
通讯作者：
Hoffmann A
影响因子：
64.8
作者：
Harris, Tajie H.;Banigan, Edward J.;Christian, David A.;Konradt, Christoph;Wojno, Elia D. Tait;Norose, Kazumi;Wilson, Emma H.;John, Beena;Weninger, Wolfgang;Luster, Andrew D.;Liu, Andrea J.;Hunter, Christopher A.
通讯作者：
Hunter, Christopher A.
影响因子：
32.4
作者：
Bannard O;Horton RM;Allen CD;An J;Nagasawa T;Cyster JG
通讯作者：
Cyster JG