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This differentiation into classically activated M1 or alternatively activated M2 macrophages is known as polarization. In this study, we isolated bone marrow-derived macrophages from \u03b22m-deficient (deficient in both MHC class Ia and Ib) and KbDb-deficient (deficient only in MHC class Ia) mice and found that \u03b22m-deficient macrophages showed a significantly lower M2b polarization efficiency. In addition, the absence of constitutive MHC class Ib expression decreased the stability of the Notch-1 intracellular domain. Finally, we found that \u03b22m-deficient mice exposed to irradiation showed reduced bacterial translocation and sepsis severity. 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