First Author | Yabas M | Year | 2011 |
Journal | Nat Immunol | Volume | 12 |
Issue | 5 | Pages | 441-9 |
PubMed ID | 21423173 | Mgi Jnum | J:171924 |
Mgi Id | MGI:5002406 | Doi | 10.1038/ni.2011 |
Citation | Yabas M, et al. (2011) ATP11C is critical for the internalization of phosphatidylserine and differentiation of B lymphocytes. Nat Immunol 12(5):441-9 |
abstractText | 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. |