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

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Abstract

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.

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Abbreviations

Ig:

Immunoglobulin

Pre-BCR:

Precursor B cell receptor

IL-7:

Interleukin-7

PS:

Phosphatidylserine

PE:

Phosphatidylethanolamine

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Acknowledgements

We thank Dr. Sebastian Herzog from the Medical University of Innsbruck, Austria, for providing wk3 cells, reagents, and his excellent advice and help during the generation of the ATP11C-deficient pre-B cell line as well as for critical reading of the manuscript. We also thank Michael Lohmüller, Felix Eichin, and Katharina Hutter from the Medical University of Innsbruck, Austria, for sharing their scientific and technical expertise.

Funding

This study was supported by the Trakya University Scientific Research Projects Coordination Unit (Project Number 2019/280).

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  1. Mehmet Yabas, Ayten Bostanci & Seda Aral

    Present address: Department of Immunology, Faculty of Medicine, Malatya Turgut Ozal University, Malatya, Turkey

Authors and Affiliations

  1. Department of Genetics and Bioengineering, Trakya University, Edirne, Turkey

    Mehmet Yabas & Ayten Bostanci

  2. Department of Biotechnology and Genetics, Institute of Natural Sciences, Trakya University, Edirne, Turkey

    Seda Aral

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Correspondence to Mehmet Yabas.

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Yabas, M., Bostanci, A. & Aral, S. ATP11C promotes the differentiation of pre-B cells into immature B cells but does not affect their IL-7-dependent proliferation. Immunol Res 71, 609–616 (2023). https://doi.org/10.1007/s12026-023-09364-6

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