Department of Genetics and Bioengineering, Trakya University, Edirne, Turkey.
Department of Immunology, Faculty of Medicine, Malatya Turgut Ozal University, Malatya, Turkey.
Immunol Res. 2023 Aug;71(4):609-616. doi: 10.1007/s12026-023-09364-6. Epub 2023 Feb 8.
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.
P4 型 ATP 酶被认为是翻转酶，能够将特定的磷脂从质膜外层向内层内化，从而有助于真核生物质膜上不对称氨基磷脂的分布。尽管人类有 14 种 P4 型 ATP 酶，老鼠有 15 种，但它们在免疫系统中的作用尚未完全了解。到目前为止，已经表明 ATP11C 对 B 细胞很重要，并且缺乏 ATP11C 的小鼠在 B 细胞发育的 pro-B 细胞到 pre-B 细胞过渡阶段发育停滞。我们使用通过 CRISPR/Cas9 工程生成的缺乏 ATP11C 的 pre-B 细胞系，在此体外测试了 ATP11C 在 pre-B 细胞中的作用，并表明 pre-B 细胞中 ATP11C 的缺失会导致翻转酶活性缺陷。我们进一步证明，ATP11C 的缺失不会阻碍 pre-B 细胞对 IL-7 的增殖反应。然而，缺乏 ATP11C 的 pre-B 细胞在去除 IL-7 后无法分化为未成熟 B 细胞。这些结果表明，pre-B 细胞中 ATP11C 的缺失破坏脂质不对称性可能控制 pre-B 细胞中从增殖到分化的转换。
