Mouse NK cell functional maturation is dependent on MHC I

NK cells effectively eliminate infected cells or tumor cells. The acquisition of cytotoxic functions occurs throughout NK cell functional maturation, a process that is commonly defined by the sequential expression of CD27 and CD11b. In addition, NK cell cytotoxicity is finely tuned by the process of education, which is dependent on MHC I. Expression of effector molecules is not impaired in NK cells from MHC I-deficient mice, but their cytotoxic activity towards target cells is reduced. While the role of MHC I on NK cell education has been extensively studied, its impact on NK cell functional maturation has not been defined. Using 2 distinct MHC I-deficient mouse models, we confirm that MHC I is not required for expression of effector molecules by NK cells. However, based on CD27 and CD11b expression, we find that fewer NK cells reach the final stage of NK cell functional maturation. Moreover, in β2m-deficient mice, early-stage NK cells express higher levels of granzyme B. Together, these findings demonstrate that NK cell functional maturation is dependent on MHC I and that the expression of effector proteins can be uncoupled from the NK cell functional maturation stages.