Mechanism of follicular trapping: localization of immune complexes and cell remnants after elimination and repopulation of different spleen cell populations

Abstract

The role of marginal zone macrophages, marginal metallophilic macrophages (marginal metallophils) and marginal zone lymphocytes in the follicular trapping of immune complexes was investigated in a detailed elimination and repopulation study. Intravenous injection of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP) resulted in a complete and lasting elimination of marginal zone macrophages and marginal metallophils, while the number of marginal zone B-lymphocytes was temporarily reduced. By means of image analysis of light-microscopic images we quantified the repopulation of the above cell types and the presence of immune complexes during the repopulation process. Trapping of peroxidase-anti-peroxidase complexes was reduced up to Day 3 after administration of Cl2MDP-liposomes, but reached control values on Day 5, before reappearance of the different cell types. Therefore, marginal zone macrophages and marginal metallophils are neither directly nor indirectly involved in the transport of immune complexes to splenic follicles. It is unlikely that marginal zone B cells play a role in the transport of complexes, as a substantial reduction in B-cell number did not impair follicular trapping. At different time-points after treatment with Cl2MDP-liposome treatment, three macrophage markers (acid phosphatase, ligand for ERTR-9 and ligand for MOMA-2) were found in splenic follicles of several animals, but not in control animals. The presence of these macrophage markers in splenic follicles implies that soluble and particulate cell remnants migrate to the follicle and are retained there without the involvement of specific antibody and complement. Collectively, the data showing trapping of immune complexes despite the absence of several candidate transporter cell types and the localization of cellular remnants to splenic follicles provide evidence against a cell-mediated transport of immune complexes. The data argue in favour of diffusion as a transport mechanism of both immune and non-immune compounds to the follicle.