Iron transport in a lymphoid cell line with the hemochromatosis C282Y mutation

The gene for hemochromatosis (HFE) is expressed in a variety of cells, incl uding those not thought to be affected by this disease. The impact of HFE o n iron transport was examined in B-lymphoid cell lines developed from a pat ient with hemochromatosis with the HFE C282Y mutation (C282Y cells) and an individual with the wild-type HFE gene (WT cells). Whereas both cell lines expressed HFE protein, C282Y cells displayed less HFE protein at the cell s urface. Transferrin receptor (TfR) number was 2- to a-fold greater in WT ce lls than in C282Y cells, while TfR affinity for transferrin (Tf) was slight ly lower in C282Y cells. TfR distribution between intracellular and cell-su rface compartments was similar in both cell lines. Iron uptake per cell was greater in WT cells but was not increased proportional to TfR number. When considered relative to cell-surface TfR number, however, iron up take and Tf internalization were actually greater in C282Y cells. Surprisingly, Tf-i ndependent iron uptake was also significantly greater in C282Y cells than i n WI cells. The ferritin content of C282Y cells was approximately 40% that of WT cells. Exposure of cells to pro-oxidant conditions in culture led to a greater inhibition of proliferation in C282Y cells than in WT cells. Our results indicate that in this B-lymphoid cell line, the HFE C282Y mutation affects both Tf-dependent and -independent iron uptake and enhances cell se nsitivity to oxidative stress. The role of HFE in iron uptake by B cells ma y extend beyond its known interaction with the TfR. (Blood, 2001;97:2734-27 40) (C) 2001 by The American Society of Hematology.