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


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.

Authors Yabas, M.; Teh, C. E.; Frankenreiter, S.; Lal, D.; Roots, C. M.; Whittle, B.; Andrews, D. T.; Zhang, Y.; Teoh, N. C.; Sprent, J.; Tze, L. E.; Kucharska, E. M.; Kofler, J.; Farell, G. C.; Broer, S.; Goodnow, C. C.; Enders, A.
Published Date 2011-03-20
Published Volume 12
Published Issue 5
Published Pages 441-9
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version