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

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

来源：Nature Immunology, 2011, 12(5): 441-U100.

DOI：10.1038/ni.2011

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.

• 出版日期2011-5
• 单位河北医科大学