TET2-mutated B- and T-cell niches within the germinal center promote T_FH lymphomagenesis. Immature B cells acquire TET2 mutations through age-related clonal hematopoiesis. This leads to clonal expansion of B cells that later acquire additional mutations such as those in core histones. These TET2-mutated B cells proliferate within the dark zone of the germinal center. As they traverse to the light zone, B cells and T cells interact with follicular dendritic cells for antigen capture and presentation. Increased CD40 expression on B cells promotes interaction and stimulation of T_FH cells via the CD40LG. T_FH lymphoma develops in niches with B cells that have features intermediate between the light and dark zones. Breaking the CD40-CD40LG interaction with anti-CD40LG inhibitory antibody reduces the growth of T_FH lymphoma and prolongs survival in mouse models of this disease.