Abstract Marginal zone (MZ) B cells are absent in CD19−/− mice. Possible causes include an intrinsic defect in B cells and/or a secondary defect in the extrinsic MZ microenvironment as a result of changes in B cell differentiation in mice lacking CD19. Cells in the MZ also include MZ macrophages (MZM) and MZ dendritic cells (DC). Although CD19 is only expressed on B cells, SIGN-R1+ MZM are absent and CD11c+ MZ DC distribution is abnormal in CD19−/− mice. Adoptively transferred B cells from normal mice are able to reconstitute MZ B cells in CD19−/− mice. In contrast, CD19−/− B cells could not enter the MZ of the normal mice. Furthermore, MZM distribution and MZ DC distribution are restored following MZ B cell reconstitution in CD19−/− mice. Thus, MZ B cells are required for MZM differentiation and MZ DC localization, but the deficiency of MZ B cells in CD19−/− mice is caused by a defect of intrinsic B cell signaling.