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

Owen M. Siggs, Carrie N. Arnold, Christoph Huber, Elaine Pirie, Yu Xia, Pei Lin, David Nemazee, Bruce Beutler

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)434-440
Number of pages7
JournalNature Immunology
Volume12
Issue number5
DOIs
Publication statusPublished - May 2011

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ASJC Scopus subject areas

  • Immunology

Cite this

Siggs, O. M., Arnold, C. N., Huber, C., Pirie, E., Xia, Y., Lin, P., ... Beutler, B. (2011). The P4-type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrow. Nature Immunology, 12(5), 434-440. https://doi.org/10.1038/ni.2012