ATP11C promotes the differentiation of pre-B cells into immature B cells but does not affect their IL-7-dependent proliferation

The P4-type ATPases are believed to function as flippases that contribute to the organization of the asymmetric aminophospholipid distribution on the plasma membranes of eukaryotes by their ability to internalize specific phospholipids from the outer leaflet to the inner leaflet. Despite the existence of 14 members of the P4-type ATPases in humans and 15 in mice, their roles in the immune system have not been fully understood. So far, ATP11C was shown to be important for B cells, and mice deficient for ATP11C had a developmental arrest at the pro-B to pre-B cell transition stage of B cell development. Using an ATP11C-deficient pre-B cell line generated through CRISPR/Cas9 engineering, we here tested the role of ATP11C in pre-B cells in vitro and showed that ablation of ATP11C in pre-B cells causes a defect in the flippase activity. We further demonstrated that loss of ATP11C does not impede the proliferation of pre-B cells in response to IL-7. However, pre-B cells lacking ATP11C failed to differentiate into immature B cells upon removal of IL-7. These results suggest that disruption of lipid asymmetry by loss of ATP11C in pre-B cells may control the switch from proliferation to differentiation in pre-B cells.

Automated summary

P4-type ATPases contribute to the asymmetrical distribution of aminophospholipids on plasma membranes in eukaryotes. However, their roles in the immune system are not well understood. By studying ATP11C-deficient pre-B cells, it was found that ATP11C is important for the flippase activity and differentiation of pre-B cells, but not their proliferation in response to IL-7. These findings suggest that ATP11C-mediated lipid asymmetry controls the switch from proliferation to differentiation in pre-B cells.