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.
authors.affiliation: Ramaciotti Immunization Genomics Laboratory, Department of Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Yabas
authors.forename: Charis E
authors.initials: CE
authors.lastname: Teh
authors.forename: Sandra
authors.initials: S
authors.lastname: Frankenreiter
authors.forename: Dennis
authors.initials: D
authors.lastname: Lal
authors.forename: Carla M
authors.initials: CM
authors.lastname: Roots
authors.forename: Belinda
authors.initials: B
authors.lastname: Whittle
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Andrews
authors.forename: Yafei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Narci C
authors.initials: NC
authors.lastname: Teoh
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sprent
authors.forename: Lina E
authors.initials: LE
authors.lastname: Tze
authors.forename: Edyta M
authors.initials: EM
authors.lastname: Kucharska
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kofler
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Farell
authors.forename: Stefan
authors.initials: S
authors.lastname: Bröer
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Goodnow
authors.forename: Anselm
authors.initials: A
authors.lastname: Enders
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D001483:Base Sequence; D002454:Cell Differentiation / Q000276:immunology*; D004705:Endocytosis / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D019254:Genes, bcl-2 / Q000276:immunology; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000276:immunology; D010768:Phosphoserine / Q000276:immunology*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015851:Interleukin-7; D012333:RNA, Messenger; D010768:Phosphoserine; D000251:Adenosine Triphosphatases