biostudies-literatureYabas MNIAID NIH HHSWellcome Trust441-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC3272780biostudies-literatureUnknown12(5)Subcompartments of the plasma membrane are believed to be critical for lymphocyte responses, but few genetic tools are available to test their function. Here we describe 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 lower rate of phosphatidylserine translocation in pro-B cells and much lower pre-B cell and B cell numbers despite expression of pre-rearranged immunoglobulin transgenes or enforced expression of the prosurvival protein Bcl-2 to prevent apoptosis and abolished pre-B cell population expansion in response to a transgene encoding interleukin 7Nature immunologyATP11C is critical for the internalization of phosphatidylserine and differentiation of B lymphocytes.PMC3272780U54 AI054523U54 AI054523-01U54 AI054523-04U54 AI054523-02U54 AI054523-03Whittle BGoodnow CCFarell GCSprent JTze LELal DEnders ARoots CMAndrews DTBroer SKucharska EMFrankenreiter SZhang YYabas MKofler JTeoh NCTeh CEfalseATP11C is critical for the internalization of phosphatidylserine and differentiation of B lymphocytes.Subcompartments of the plasma membrane are believed to be critical for lymphocyte responses, but few genetic tools are available to test their function. Here we describe 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 lower rate of phosphatidylserine translocation in pro-B cells and much lower pre-B cell and B cell numbers despite expression of pre-rearranged immunoglobulin transgenes or enforced expression of the prosurvival protein Bcl-2 to prevent apoptosis and abolished pre-B cell population expansion in response to a transgene encoding interleukin 72011-01-01T00:00:00Z2011 May2025-04-18T19:53:27.637Z2019-03-27T00:48:46ZS-EPMC32727802142317310.1038/ni.2011