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

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

Author information

  • 1Ramaciotti Immunization Genomics Laboratory, Department of Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.

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.

Comment in

  • B cells need their flip-flops. [Immunol Cell Biol. 2011]
  • Flippin' lipids. [Nat Immunol. 2011]
PMID:
21423173
[PubMed - indexed for MEDLINE]
PMCID:
PMC3272780
Free PMC Article

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