ATP11C is critical for the internalization of phosphatidylserine and differentiation of B lymphocytes

Nat Immunol. 2011 May;12(5):441-9. doi: 10.1038/ni.2011. Epub 2011 Mar 20.


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 types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / immunology*
  • Animals
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology*
  • Base Sequence
  • Cell Differentiation / immunology*
  • Endocytosis / immunology*
  • Female
  • Flow Cytometry
  • Genes, bcl-2 / immunology
  • Interleukin-7 / genetics
  • Interleukin-7 / immunology
  • Liver / cytology
  • Liver / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Knockout
  • Mice, Transgenic
  • Molecular Sequence Data
  • Mutagenesis / immunology
  • Phosphoserine / immunology*
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction


  • Interleukin-7
  • RNA, Messenger
  • Phosphoserine
  • Adenosine Triphosphatases