B-cell development requires a specific distribution of membrane phospholipids. Mutations in enzymes mediating phospholipid transport can cause immunodeficiency.

Aminophospholipid flippases mediate the exchange of phospholipids from one leaflet of the plasma membrane to the other. We have recently identified a previously unknown X-linked B cell-deficiency syndrome in mice caused by mutations in Atp11c, which encodes a member of the P4 ATPase family thought to serve as 'flippases' that concentrate aminophospholipids in the cytoplasmic leaflet of cell membranes. Defective ATP11C resulted in a defect of B-cell development and very low B cell numbers. In the project we want to characterise the function of ATP11c following expression in mammalian cells and identify the mechanism by which the mutation abolishes B-cell development.