T滤泡辅助细胞在体液免疫反应中暂时解锁生发中心B细胞的可塑性状态，这一成果由Sanford I. Weill医学院Effie Apostolou小组经过不懈努力而取得。该研究于2025年12月29日发表于国际一流学术期刊《自然—细胞生物学》杂志上。

在这里，该课题组人员报告GC B细胞，不像其他成熟的B细胞，暂时获得独特的表观遗传可塑性，证明了他们的能力增强重编程诱导多能干细胞。这种可塑性取决于T滤泡辅助细胞（T_FH），而不是由于增殖增加或MYC激活。相反，它涉及到B细胞身份的减弱以及NF-κB和其他T_FH衍生信号驱动的干细胞和祖细胞程序的抑制。因此，生理GC可塑性受到正选择亲和成熟过程的严格约束。组蛋白1（一种限制胚胎干细胞程序可及性的染色质压实调节因子）的缺失通过绕过这一守门机制进一步增强了GC的可塑性。重要的是，富含GC可塑性特征的B细胞淋巴瘤患者预后较差，表明该机制也可能有助于淋巴瘤的发生。

据悉，在生发中心（GC）反应过程中，成熟的B细胞经历快速可逆的表型变化，这对适应性免疫至关重要。

附：英文原文

Title: T follicular helper cells transiently unlock a plasticity state in germinal centre B cells during the humoral immune response

Author: Scourzic, Laurianne, Izzo, Franco, Teater, Matt, Polyzos, Alexander P., Cucereavii, Lucretia, Chin, Christopher R., Papin, Antonin, Pinto, Hugo B., Mlynarczyk, Coraline, Tsialta, Ioanna, Xia, Min, Lidoski, Abigail, Myers, Robert M., Israel, Eva M., Venturutti, Leandro, Mackay, Simon P., Hoehn, Kenneth B., Skoultchi, Arthur I., Bguelin, Wendy, Stadtfeld, Matthias, Chen, Zhengming, Landau, Dan A., Melnick, Ari M., Apostolou, Effie

Issue&Volume: 2025-12-29

Abstract: During the germinal centre (GC) reaction, mature B cells undergo rapid and reversible phenotypic shifts that are essential for adaptive immunity. Here we report that GC B cells, unlike other mature B cells, transiently acquire a unique epigenetic plasticity, demonstrated by their enhanced capacity to reprogram to induced pluripotent stem cells. This plasticity depends on T follicular helper (TFH) cells and is not due to increased proliferation or MYC activation. Instead, it involves weakening of B-cell identity and derepression of stem and progenitor programs driven by NF-κB and other TFH-derived signals. Thus, physiological GC plasticity is tightly constrained by the affinity maturation process of positive selection. Loss of histone 1, a chromatin compaction regulator restricting the accessibility of embryonic stem cell programs, further enhances GC plasticity by bypassing this gatekeeping mechanism. Importantly, patients with B-cell lymphoma enriched for GC plasticity signatures had worse outcomes, suggesting that this mechanism may also contribute to lymphomagenesis.

DOI: 10.1038/s41556-025-01833-4

Source: https://www.nature.com/articles/s41556-025-01833-4