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

B lymphopoiesis begins in fetal liver, switching to bone marrow after birth 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 a cell-intrinsic arrest of adult B lymphopoiesis. Mutant fetal liver progenitors generated B cells in situ, but not in irradiated adult bone marrow, highlighting a necessity for the affected pathway only in the context of adult bone marrow. The causative mutation was 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.