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- Title
ATP11C is critical for the internalization of phosphatidylserine and differentiation of B lymphocytes.
- Authors
Yabas, Mehmet; Teh, Charis E; Frankenreiter, Sandra; Lal, Dennis; Roots, Carla M; Whittle, Belinda; Andrews, Daniel T; Zhang, Yafei; Teoh, Narci C; Sprent, Jonathan; Tze, Lina E; Kucharska, Edyta M; Kofler, Jennifer; Farell, Geoffrey C; Bröer, Stefan; Goodnow, Christopher C; Enders, Anselm
- Abstract
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 7. The only other abnormalities we noted were anemia, hyperbilirubinemia and hepatocellular carcinoma. Our results identify an intimate connection between phospholipid transport and B lymphocyte function.
- Publication
Nature immunology, 2011, Vol 12, Issue 5, p441
- ISSN
1529-2916
- Publication type
Journal Article
- DOI
10.1038/ni.2011