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. © 2011 Nature America, Inc. All rights reserved.
CITATION STYLE
Yabas, M., Teh, C. E., Frankenreiter, S., Lal, D., Roots, C. M., Whittle, B., … Enders, A. (2011). ATP11C is critical for the internalization of phosphatidylserine and differentiation of B lymphocytes. Nature Immunology, 12(5), 441–449. https://doi.org/10.1038/ni.2011
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