H-ferritin (red) binds to TIM-2 (green) and triggers endocytosis of the receptor–ligand pair (yellow).

Chen et al. now show that although TIM-2 is most highly expressed in the liver, the primary iron storage organ, this protein is also found on splenic B cells. TIM-2 expression was particularly high on germinal center B cells that were actively responding to antigenic stimulation. Using a TIM-2 reporter cell line, they showed that a soluble product of activated macrophages bound to TIM-2. That product was H-ferritin. Binding triggered endocytosis of the receptor–ligand pair, suggesting that the interaction was functional.

The authors are now investigating the consequences of the ferritin–TIM-2 interaction. A recent study showed that intracellular H-ferritin is required for the antiapoptotic effect of NF-B activation in fibroblasts, prompting Seaman to speculate that H-ferritin uptake in activated germinal center B cells might have a similar antiapoptotic effect.