LYMPHOID NEOPLASIA CD 10 delineates a subset of human IL-4 producing follicular helper T cells involved in the survival of follicular lymphoma B cells

• CD10 identifies a unique subset of fully functional germinal center TFH that are activated and amplified within the FL cell niche. • FL CD10 TFH specifically display an IL-4IFN-g cytokine profile and encompass the malignant B-cell-supportive TFH subset. 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 FL-TFH specifically exhibit an IL-4IFN-gTNF-a cytokineprofile associatedwith a high capacity to sustaindirectly and indirectly malignant B-cell survival. Altogether, our results highlight the important role of this novel functional subset in the FL cell niche. (Blood. 2015;125(15):2381-2385)