The P4-type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrow

Department of Genetics, The Scripps Research Institute, La Jolla, California, USA.
Nature Immunology (Impact Factor: 20). 03/2011; 12(5):434-40. DOI: 10.1038/ni.2012
Source: PubMed


B lymphopoiesis begins in the fetal liver, switching after birth to the bone marrow, where it persists for life. The unique developmental outcomes of each phase are well documented, yet their molecular requirements are not. Here we describe two allelic X-linked mutations in mice that caused cell-intrinsic arrest of adult B lymphopoiesis. Mutant fetal liver progenitors generated B cells in situ but not in irradiated adult bone marrow, which emphasizes a necessity for the affected pathway only in the context of adult bone marrow. The causative mutations were ascribed to Atp11c, which encodes a P4-type ATPase with no previously described function. Our data establish an essential, cell-autonomous and context-sensitive function for ATP11C, a putative aminophospholipid flippase, in B cell development.

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Available from: Owen M Siggs
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    • "The difference to our previous observation is most likely caused by the use of a more sensitive analogue (C 6 - NBD-PS) that differs from the original C 12 -NBD-PS ligand by the length of the sn-2 chain to which the NBD fluorescence marker is attached. The shorter sn-2 chain increases flippasemediated transbilayer movement and allows back-extraction using fatty acid free BSA[30]ATP11C-deficient animals have a specific defect in early B cell development in the bone marrow[20,21]. One explanation for the pro-B cell specific defect in development despite the widespread loss of flippase activity in immune cell subsets could be that these cells rely more on flippase activity compared to other cells because of an intrinsically increased PS externalization . "
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