Disruption of the lymphoid structure after 7 days of sustained TLR7 stimulation. Spleen cryosections of C57BL/6 mice treated for 7 days with R848. (A) Applied dose correlated with malformation of splenic lymphoid follicles with enlarged T- (CD4 and CD8) and B- (B220) cell zones, and reduced marginal zone B lymphocytes (B220 and CD21/35; arrowhead). (B) MOMA-1⁺ and F4/80⁺ macrophages were not affected. (C) PNA⁺ germinal centers (arrowheads) and FDC-M1⁺ networks were reduced at day 7 but not at day 21 or 42 of treatment. R848 concentrations were as indicated (mg/kg per day). N ≥ 3.