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Updated: Apr 27, 2026

Natural Killer NK and CAR-NK Cell Expansion Method using Membrane Bound-IL-21-Modified B Cell Line
Published on: February 8, 2022
Mature resting Ly6C(high) natural killer cells can be reactivated by IL-15
Ai Omi1, Yutaka Enomoto, Tsuyoshi Kiniwa
1Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
Insights
Mature natural killer (NK) cells exhibit plasticity, with Ly6C(high) NK cells representing a resting subset that can be activated to Ly6C(low) effector cells. This plasticity is crucial for mounting effective immune responses during infection.
Area of Science:
- Immunology
- Cell Biology
Background:
- Mature natural killer (NK) cells display heterogeneity in cell surface molecule expression, but the functional implications of these subsets are not fully elucidated.
- Understanding NK cell heterogeneity is key to comprehending their roles in immune surveillance and response.
Purpose of the Study:
- To investigate the functional differences and physiological roles of distinct NK cell subsets.
- To characterize the Ly6C(low) and Ly6C(high) NK cell subsets in C57BL/6 mice.
Main Methods:
- Flow cytometry to identify and sort Ly6C(low) and Ly6C(high) NK cell subsets.
- Assessment of cytokine production (IFN-γ) and cytotoxic potential (granzyme B).
- Adoptive transfer experiments and in vitro/in vivo stimulation with IL-15, polyI:C, and CpG.
Main Results:
- C57BL/6 murine NK cells can be divided into Ly6C(low) and Ly6C(high) subsets based on Ly6C expression.
- Ly6C(high) NK cells are characterized by lower IFN-γ and granzyme B production and reduced proliferative capacity, indicating a resting state.
- Ly6C(high) NK cells are derived from Ly6C(low) NK cells in vivo and can be activated to Ly6C(low) effector cells upon IL-15 stimulation, both in vitro and in vivo.
Conclusions:
- Mature NK cells exhibit significant plasticity, with Ly6C(high) cells serving as a reservoir of resting cells.
- This plasticity allows for a rapid and robust NK cell response upon encountering inflammatory stimuli like IL-15.
- The Ly6C(high) to Ly6C(low) transition is a critical mechanism for effective immune responses to infections.
Abstract:
Mature NK cells are heterogeneous as to their expression levels of cell surface molecules. However, the functional differences and physiological roles of each NK-cell subset are not fully understood. In this study, we report that based on the Ly6C expression levels, mature C57BL/6 murine NK cells can be subdivided into Ly6C(low) and Ly6C(high) subsets. Ly6C(high) NK cells are in an inert state as evidenced by the production of lower levels of IFN-γ and granzyme B, and they exhibit poorer proliferative potential than Ly6C(low) NK cells. In addition, adoptive transfer experiments revealed that Ly6C(high) NK cells are derived from Ly6C(low) NK cells in the steady state. These results strongly suggest that Ly6C(high) NK cells are resting cells in the steady state. However, in vitro, Ly6C(high) NK cells become Ly6C(low) NK cells with strong effector functions upon stimulation with IL-15. Moreover, Ly6C(high) NK cells also revert to Ly6C(low) NK cells in vivo upon injection of the IL-15 inducers polyI:C and CpG. Taken together, these results demonstrate the plasticity of mature NK cells and suggest that Ly6C(high) NK cells are a reservoir of potential NK cells that allow effective and strong response to infections.
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