Delineation of the Human Germinal Centre Immune Landscape Using Multiplex Imaging Analysis.

IF 4.9 3区医学 Q2 IMMUNOLOGY

Immunology Pub Date : 2025-05-27 DOI:10.1111/imm.13955

Spiros Georgakis, Michail Orfanakis, Craig Fenwick, Cloe Brenna, Simon Burgermeister, Helen Lindsay, Giuliana Xavier de Medeiros, Fernanda Romano Bruno, Susan Pereira Ribeiro, Raphael Gottardo, Giuseppe Pantaleo, Constantinos Petrovas

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引用次数: 0

Abstract

Given the role of follicular immune dynamics, especially the germinal centre, for the development of pathogen-specific antibodies, their in situ characterisation is of great importance. We have developed a multiplex immunofluorescence imaging pipeline that allows the analysis of human follicular adaptive and innate immune cell subsets. Our data revealed the in situ phenotypic heterogeneity and differential localisation of follicular helper CD4 T (T_FH) cell subsets across follicular areas in tonsils and reactive lymph nodes (LNs). Cell clustering analysis identified specific T_FH subsets with differential prevalence between tonsils and LNs. Further, a multiplex RNAscope/protein imaging assay revealed the functional heterogeneity of T_FH cells. No significant differences in follicular innate immune cell densities were found between tonsils and LNs. In conclusion, we present a combinatory experimental approach that provides a comprehensive analysis of human follicular and/or germinal centre immune dynamics and could be used to further understand the pathogenesis of diseases such as HIV and lymphomas.

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利用多重成像分析描绘人类生发中心免疫景观。

鉴于滤泡免疫动力学的作用，特别是生发中心，对病原体特异性抗体的发展，它们的原位表征是非常重要的。我们已经开发了一种多重免疫荧光成像管道，允许分析人类滤泡适应性和先天免疫细胞亚群。我们的数据揭示了滤泡辅助CD4 T （TFH）细胞亚群在扁桃体和反应性淋巴结（LNs）滤泡区域的原位表型异质性和差异定位。细胞聚类分析确定了扁桃体和LNs之间具有不同患病率的特定TFH亚群。此外，多重RNAscope/蛋白成像分析揭示了TFH细胞的功能异质性。滤泡先天免疫细胞密度在扁桃体和LNs之间无显著差异。总之，我们提出了一种组合实验方法，提供了对人类卵泡和/或生发中心免疫动力学的全面分析，并可用于进一步了解诸如艾滋病毒和淋巴瘤等疾病的发病机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunology 医学-免疫学

CiteScore

11.90

自引率

1.60%

发文量

175

审稿时长

4-8 weeks

期刊介绍： Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers. Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology. The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.