Intravital single-cell behavior profiling reveals disrupted germinal center B cell motility and interactions by EZH2 gain-of-function mutation
Min, C.; Choe, K.; Chen, X.; Karagiannidis, I.; Sivakumar, N.; Xu, C.; Melnick, A.; Phillip, J. M.; Beguelin, W. · immunology · 2026-09-06 · 原文
DOI：10.64898/2026.09.02.748910作者：9 位
Germinal center (GC) B-cells give rise to the majority of non-Hodgkin lymphomas, underscoring the need to pinpoint critical processes that initiate and drive lymphomagenesis. Lymphoma driver mutations can alter GC B cell functions and B cell fate decisions. Here, we studied how EZH2 oncogenic mutation in GC B cells alters cellular motility and interactions with T follicular helper (Tfh) cells and follicular dendritic cells (FDCs) to determine B cell fate. By combining intravital imaging, single-cell behavior analyses, and RNA sequencing, we uncover how lymphoma-associated EZH2 mutations reprogram the behaviors of GC B cells in vivo. We found that EZH2 mutations increased single-cell motility speeds and morphological plasticity of GC B cells, redirecting migration toward the FDC-rich light zone subregions rather than to the dark zone. Although mutant EZH2 GC B cells exhibited normal engagement quality with FDCs, they showed shorter interaction times and reduced surface engagement with Tfh cells. Notably, EZH2 mutant B cells required prior contact with FDC before engaging with Tfh cells, thus impairing DZ recycling. This motility phenotype scaled with local mutant clone abundance, su
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1. 人话版
Germinal center (GC) B-cells give rise to the majority of non-Hodgkin lymphomas, underscoring the need to pinpoint critical processes that initiate and drive lymphomagenesis.
Lymphoma driver mutations can alter GC B cell functions and B cell fate decisions.
2. 领域脉络
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3. 机制拆解
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4. 证据与数字
Here, we studied how EZH2 oncogenic mutation in GC B cells alters cellular motility and interactions with T follicular helper (Tfh) cells and follicular dendritic cells (FDCs) to determine B cell fate.
By combining intravital imaging, single-cell behavior analyses, and RNA sequencing, we uncover how lymphoma-associated EZH2 mutations reprogram the behaviors of GC B cells in vivo.
We found that EZH2 mutations increased single-cell motility speeds and morphological plasticity of GC B cells, redirecting migration toward the FDC-rich light zone subregions rather than to the dark zone.
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