Loss of TFH immune synapse formation and gain of FDC interactions with EZH2 mutations. (A) EZH2 wild-type B cells undergo normal clonal selection by binding antigen on FDCs and presenting it on MHC class II. Those with the highest antigen affinity and presentation form an immune synapse with TFH cells, leading to CD40/CD40L signaling, which stimulates terminal differentiation or DZ recycling. (B) EZH2 mutant B cells have reduced MHC expression and immune synapse formation with TFH cells that leads to decreased CD40/CD40L signaling and DZ recycling. However, these cells are able to proliferate and survive through interactions with an expanded network of FDCs.