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

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.

SUBMITTER: Siggs OM

PROVIDER: S-EPMC3079768 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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

Siggs Owen M OM Arnold Carrie N CN Huber Christoph C Pirie Elaine E Xia Yu Y Lin Pei P Nemazee David D Beutler Bruce B

Nature immunology 20110320 5

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 ...[more]

PMID: 21423172

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