The roles of Notch1 and Notch2 in T-cell function have been well studied, but the functional roles of Notch in B cells have not been extensively investigated, except for Notch2 involvement in peripheral marginal zone B-cell differentiation. This study examined the roles of Notch1 in murine primary B cells. During B-cell activation by B-cell receptor ligation, Notch1 was up-regulated while Notch2 was not. In addition, Notch1 up-regulation itself did not contribute to the further activation of B cells, but the Notch ligand was important for Notch1-mediated further B-cell activation. Moreover, Notch1 deficiency significantly decreased B-cell activation and antibody secretion under the presence of Notch ligand. These data suggest that Notch1 is an important mediator for enhancing B-cell activation and antibody secretion by Notch ligand.