Anti-ICOSL administration was only protective when there was an accumulation of TFH cells in the absence of MZB cells9 or Qa1 CD8+ TREGs.46 Although more circuitous than the ICOS blockade that also depletes TFH cells,49 recombinant ICOS-Fc chimera immunization to provoke endogenous ICOS blocking antibody production increased early atherosclerosis in Apoe−/− mice.50 Accordingly, we conclude that the TFH-MZB interaction is atheroprotective and is necessary to maintain a balance between the extrafollicular IgM antibody production and GC responses in atherosclerosis (Figure). Here, ICOSLG is linked to atherosclerosis.