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

Mehmet Yabas; Charis E. Teh; Sandra Frankenreiter; Dennis Lal; Carla M. Roots; Belinda Whittle; Daniel T. Andrews; Yafei Zhang; Narci C. Teoh; Jonathan Sprent; Lina E. Tze; Edyta M. Kucharska; Jennifer Kofler; Geoffrey C. Farell; Stefan Bröer; Christopher C. Goodnow; Anselm Enders

doi:10.1038/ni.2011

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

Mehmet Yabas, Charis E. Teh, Sandra Frankenreiter, Dennis Lal, Carla M. Roots, Belinda Whittle, Daniel T. Andrews, Yafei Zhang, Narci C. Teoh, Jonathan Sprent, Lina E. Tze, Edyta M. Kucharska, Jennifer Kofler, Geoffrey C. Farell, Stefan Bröer, Christopher C. Goodnow, Anselm Enders

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109 Citations (Scopus)

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.

Original language	English
Pages (from-to)	441-449
Number of pages	9
Journal	Nature Immunology
Volume	12
Issue number	5
DOIs	https://doi.org/10.1038/ni.2011
Publication status	Published - May 2011

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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., Bröer, S., Goodnow, C. C., & 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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title = "ATP11C is critical for the internalization of phosphatidylserine and differentiation of B lymphocytes",

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.",

author = "Mehmet Yabas and Teh, {Charis E.} and Sandra Frankenreiter and Dennis Lal and Roots, {Carla M.} and Belinda Whittle and Andrews, {Daniel T.} and Yafei Zhang and Teoh, {Narci C.} and Jonathan Sprent and Tze, {Lina E.} and Kucharska, {Edyta M.} and Jennifer Kofler and Farell, {Geoffrey C.} and Stefan Br{\"o}er and Goodnow, {Christopher C.} and Anselm Enders",

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Yabas, M, Teh, CE, Frankenreiter, S, Lal, D, Roots, CM, Whittle, B, Andrews, DT, Zhang, Y, Teoh, NC, Sprent, J, Tze, LE, Kucharska, EM, Kofler, J, Farell, GC, Bröer, S, Goodnow, CC & Enders, A 2011, 'ATP11C is critical for the internalization of phosphatidylserine and differentiation of B lymphocytes', Nature Immunology, vol. 12, no. 5, pp. 441-449. https://doi.org/10.1038/ni.2011

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AU - Kucharska, Edyta M.

AU - Kofler, Jennifer

AU - Farell, Geoffrey C.

AU - Bröer, Stefan

AU - Goodnow, Christopher C.

AU - Enders, Anselm

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

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