An immunoassay for human serum hepcidin at last: Ganz klar?

The WASP gene is located on the X chromosome. Random X chromosome inactivation in WASp ϩ/-mice would theoretically result in 50% of cells expressing WASp. Westerberg et al show this to be the case in the myeloid compartment , that is, neutrophils, dendritic cells, macro-phages, and NK cells. Also, both papers show that in the most immature subsets of T and B cells, such as the double-negative or double-positive thymocytes and the pro-B, pre-B, and immature B cells in the bone marrow, there is no selective advantage for WASp expression. In contrast, in the more mature T and B cells, WASp positive cells had a strong selective advantage (the different stages of B-cell differentiation are shown in the figure). As differentiation proceeds, the advantage of WASp ϩ cells increases. The strongest advantage for WASp expression was found in regulatory T cells and natural killer T cells in spleen and thymus, and in splenic marginal zone (MZ) B cells, in which at least 80% of the cells expressed WASp. In addition, WASp ϩ germinal center B cells had a more pronounced selective advantage than nongerminal center cells. In a particular subpopulation of B cells called B1 cells that reside in the peritoneal cavity, WASp expressing cells were dominant. Finally, in a WAS patient with a revertant mutation, there was evidence for selective advantage of mature peripheral B cells. Meyer-Bahlburg et al investigated the presence of various subpopulations of B cells in wild-type or WASp-deficient mice. No significant differences were observed in the early populations of pro-B cells to immature B cells, whereas the more mature B-cell populations, that is, IgD ϩ cells in the bone marrow, the follicular and MZ B cells in the spleen were reduced in numbers in mice lacking WASp. In addition, they found that in wild-type mice the mature B-cell subpopulations expressed relatively more WASp as compared with immature B cells. With reconstitution experiments, the scientists concluded that the relative absence of the WASp negative MZ B cells was due to an intrinsic B-cell deficiency. They went on to analyze the capacity of the cells to divide and found that, surprisingly, the follicular and MZ WASp-B cells had an increased turnover rate as compared with wild-type cells. Thus, the deficiency in the more mature B-cell populations is due to an altered homeostasis and not to a differentiation defect. No evidence was found for an increased rate of …