Background: Millions of people in the world are suffering from atopic dermatitis (AD), which is a chronic inflammatory skin disease triggered by Th2 immune responses. The NC/Nga mouse is the most extensively studied animal model of AD. Like human AD, NC/Nga mice demonstrate increased levels of IgE, a hallmark of Th2 immune responses. Adaptive immunity cannot be generated without help of innate immunity. Especially natural killer T (NKT) cells and marginal zone B (MZB) cells have been known to play important roles in linking innate immunity to adaptive immunity. Methods: Through flow cytometric analysis and ELISA assay, we investigated whether these lymphocytes might be altered in number in NC/Nga mice. Results: Our data demonstrated that the number of NKT cells was reduced in NC/Nga mice and IFN${gamma}$ production by NKT cells upon ${alpha}-GalCer$ stimulation decreased to the levels of CD1d KO mice lacking in NKT cells. However, reduction of NKT cells in NC/Nga mice was not due to CD1d expression, which was normal in the thymus. Interestingly, there was a significant increase of $CD1d^{high}B220^+$ cells in the spleen of NC/Nga mice. Further, we confirmed that $CD1d^{high}B220^+$ cells are B cells, not dendritic cells. These $CD1d^{high}B220^+$ B cells show $IgM^{high}CD21^{high}CD23^{low}$, a characteristic phenotype of MZB cells. Conclusion: We provide the evidence that there are decreased activities of NKT cells and increased number of MZB cells in the NC/Nga mice. Our findings may thus explain why NC/Nga mice are susceptible to AD.