The marginal zone (MZ) of the mouse spleen contains macrophages that express receptors that trap pathogens, including the scavenger receptor macrophage receptor with a collagenous structure and the C-type lectin specific intracellular adhesion molecule-grabbing nonintegrin receptor 1 (SIGN-R1). We previously reported that expression of SIGN-R1 was decreased in CD19-deficient mice. In this study, we demonstrate that SIGN-R1 is expressed on a subset of macrophage receptor with a collagenous structure (MARCO)+ macrophages. This subset is diminished when MZ B cells are absent due to either genetic developmental defects or following transient migration of B cells out of the MZ. When B cells return to the MZ, there is a delay in recovery of SIGN-R1–expressing macrophages. During this period, capture of Ficoll, which for the macrophages requires SIGN-R1, remains defective not only by the macrophages, but also by the B cells. Thus, MZ B cells regulate expression of molecules on macrophages that are important for trapping Ag, which, in turn, is required for Ag capture by the B cells.

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.

Germinal centers (GC) are sites within secondary lymphoid organs where affinity maturation and somatic hypermutation occur, producing high affinity antibody forming cells and memory B cells. We reported previously that mice with mutant CD19 form GC with dark and light zones, although GC B cell differentiation and proliferation are defective in the light zone of these mice. We now show that PNA+ B cells are induced after SRBC immunization and form a dark zone but fail to enter the FDC (light) zone in mice that lack CD19. These mice also lack marginal zone (MZ) B cells, which have been reported to contribute to GC responses through delivery of immune complexes to follicular dendritic cells (FDC), suggesting a possible link between the lack of MZ B cells and the impaired GC reaction. Therefore, we compared GC in the spleen with those in the LN, which does not have a MZ. We used induction of VCAM-1 expression as a marker for FDC activation. Immunization of CD19-deficient mice induced expression of VCAM-1 on LN FDC. In contrast, induction of VCAM-1 expression on FDC in splenic GC was severely reduced in the same mice. These data suggest distinct mechanisms for FDC activation in the LN, which is independent of CD19 on B cells, and in the spleen. In contrast to the LN, immunization fails to activate FDC in splenic GC in CD19-deficient mice, which leads to defective light zone formation. These and other data suggest that the deficiency of MZ B cells and the failure to activate FDC in mice that lack CD19 may be linked: MZ B cells may play a vital role in activation of FDC in splenic follicles that is critical for GC function. Supported by NIH R01 AI42265.