Fig. 1

Epigenetic dysregulation in FL modifies its microenvironment. Somatic mutations occur during the early steps of FL lymphomagenesis (dashed circle, 1). Accumulation of genetic and epigenetic mutations promotes tumor progression. All these alterations accumulate during the different phases of the GC reaction, contributing to the dysfunctional B-T cell crosstalk (dashed circle, 2) that favors tumor growth, escape, and dissemination. 1- Schematic summary of the epigenetic regulators frequently mutated in FL: CREBBP, KMT2D and EZH2. These mutations occur concurrently in most FL, but it is not known whether they act alone or cooperatively in driving B cell malignancy and in shaping the FL epigenome. H3Kac, histone H3 lysine acetylation; H3K4me3, histone H3 lysine 4 trimethylation; H3K27me3, histone H3 lysine 27 trimethylation. Loss-of-function: -, gain-of-function: + . 2- Consequences of epigenetic gene mutations on the immunological synapse. Impact of CREBBP, KMT2D and EZH2 gene mutations in FL B cells on the crosstalk of tumor cells, T follicular helper (TFH) cells, and follicular dendritic cells (FDC). Alterations of this cross-talk lead to inhibition of TFH immune synapse formation and antigen presentation, and increased FDC interactions. Specifically, CREBBP gene mutations affect antigen presentation, and KMT2D and EZH2 gene mutations lead to a disrupted immune synapse. Red stars: decreased expression. Green stars: increased expression. Dashed arrows: abnormal pathway