Amé-Thomas Patricia, Hoeller Sylvia, Artchounin Catherine, Misiak Jan, Braza Mounia Sabrina, Jean Rachel, Le Priol Jérôme, Monvoisin Céline, Martin Nadine, Gaulard Philippe, Tarte Karin
INSERM, Unité Mixte de Recherche U917, Equipe Labellisée Ligue Contre le Cancer, Rennes, France; Université Rennes 1, Unité Mixte de Recherche U917, Rennes, France; Etablissement Français du Sang Bretagne, Rennes, France; Centre Hospitalier Universitaire de Rennes, Service d'Immunologie, Thérapie Cellulaire et Hématopoïèse, Rennes, France;
Institute for Pathology, University Hospital Basel, Switzerland; INSERM U955, Créteil, France; Université Paris-Est, Créteil, France; and.
Blood. 2015 Apr 9;125(15):2381-5. doi: 10.1182/blood-2015-02-625152. Epub 2015 Mar 2.
In follicular lymphoma (FL), follicular helper T cells (TFH) have been depicted as one of the main components of the malignant B-cell niche and a promising therapeutic target. Although defined by their capacity to sustain FL B-cell growth together with specific gene expression and cytokine secretion profiles, FL-TFH constitute a heterogeneous cell population. However, specific markers reflecting such functional heterogeneity are still lacking. In this study, we demonstrate that CD10 identifies a subset of fully functional germinal center TFH in normal secondary lymphoid organs. Importantly, this subset is amplified in the FL context, unlike in other B-cell lymphomas with a follicular growth pattern. Furthermore, whereas FL-TFH produce high levels of interleukin (IL)-21 and low levels of IL-17 irrespectively of their CD10 expression, CD10(pos) FL-TFH specifically exhibit an IL-4(hi)IFN-γ(lo)TNF-α(hi) cytokine profile associated with a high capacity to sustain directly and indirectly malignant B-cell survival. Altogether, our results highlight the important role of this novel functional subset in the FL cell niche.
在滤泡性淋巴瘤（FL）中，滤泡辅助性T细胞（TFH）被认为是恶性B细胞微环境的主要组成部分之一，也是一个有前景的治疗靶点。尽管FL-TFH可通过其维持FL B细胞生长的能力以及特定的基因表达和细胞因子分泌谱来定义，但它们构成了一个异质性细胞群体。然而，目前仍缺乏反映这种功能异质性的特异性标志物。在本研究中，我们证明CD10可识别正常二级淋巴器官中具有完全功能的生发中心TFH亚群。重要的是，与其他具有滤泡生长模式的B细胞淋巴瘤不同，该亚群在FL环境中会扩增。此外，尽管FL-TFH无论其CD10表达如何都会产生高水平的白细胞介素（IL）-21和低水平的IL-17，但CD10阳性的FL-TFH特别表现出IL-4高、IFN-γ低、TNF-α高的细胞因子谱，这与直接和间接维持恶性B细胞存活的高能力相关。总之，我们的结果突出了这一新的功能亚群在FL细胞微环境中的重要作用。
