Humoral immune responses against particulate bacterial antigens are dependent on marginal metallophilic macrophages in the spleen

Lymphoid organs are populated by different macrophage subpopulations. In the spleen, four subpopulations can be characterized using differences in, for example, morphology, localization, cell markers and repopulation kinetics after liposome-mediated depletion. The involvement of the different macrophage subpopulations in the immune response to particulate antigens was studied in vivo by intravenous injection of clodronate containing liposomes to eliminate the splenic macrophages, followed by immunization with trinitrophenylated Brucella abortus (TNP-BA; thymus-independent (TI)) or TNP-Lactobacillus acidophilus (TNP-LB; thymus-dependent (TD)) at different time intervals. A strong decrease in the number of antibody-secreting cells (ASC) against TNP-LB was measured after elimination of all splenic macrophages. When TNP-LB was injected after repopulation of the red pulp macrophages (completed after 2 weeks), the ASC response was still strongly reduced. Restoration of the capacity to mount an immune response correlated well with the reappearance of the marginal metallophilic macrophages. It is concluded that this particular subset of macrophages is involved in the immune response to these particulate bacterial TD antigens. In contrast, the response against the particulate bacterial TI antigen TNP-BA was not impaired after depletion of splenic macrophages, although apparent changes in IgG isotypes were observed.