Marginal zone macrophages and their role in the immune response against T‐independent type 2 antigens: modulation of the cells with specific antibody

Abstract

Marginal zone macrophages are strategically positioned in the marginal zone of the spleen and are thought to play an important role in the initiation of the immune response to T-independent type 2 responses. The cells are characterized by high phagocytic activity and by the selective uptake of neutral polysaccharides. In the mouse marginal zone macrophages react specifically with the monoclonal antibody ER-TR9. Injection of the antibody resulted in a complete abrogation of the uptake of neutral polysaccharides by the cells in vivo, although the cells were still capable of taking up latex and carbon particles. The complete blockade of the polysaccharide uptake did not result in an altered humoral immune response against this antigen. When the antibody ER-TR9 was coupled to the toxin gelonin a complete elimination of the marginal zone macrophages could be established in vivo. However, complete elimination did not result in changes of the immune responses against 2,4,6-trinitrophenylated Ficoll, suggesting that the marginal zone macrophages are either not involved in this type of response, or that their function can be taken over by other cells. The possible role of these cells and the importance of the spleen in the immune response against bacterial antigens is discussed.

Parameters Underlying Distinct T Cell-Dependent Polysaccharide-Specific IgG Responses to an Intact Gram-Positive Bacterium versus a Soluble Conjugate Vaccine

“…Particulation (27,28) as well as components of the bacterial surface interacting with scavenger receptors (29) and complement components (30) could affect both the cell type-specific internalization and cellular trafficking of Ag within the secondary lymphoid organ, with a consequent impact on the functional outcome of the immune response. The propensity of particulate Ags to be sequestered within the marginal zone (MZ) (28), and the observation that MZBs in relation to FB are programmed to favor plasma cell over memory cell differentiation (22), led us to hypothesize that the failure of intact Pn to generate PPS14-specific IgG memory was secondary to its selective usage of MZBs to generate this response. Indeed, we show that the PPS14-specific IgG response to intact Pn14, but not conjugate, is markedly reduced in Lsc Ϫ/Ϫ mice, in which MZBs are defective in migrating from the MZ and are thus unable to receive CD4 ϩ T cell help (7,10).…”

The C-type lectin SIGN-R1 mediates uptake of the capsular polysaccharide ofStreptococcus pneumoniaein the marginal zone of mouse spleen

“…A critical role of the spleen is the formation of antibodies by marginal zone B cells (13)(14)(15), particularly complement-fixing antibodies (16)(17)(18)(19)(20). The role of macrophages in the processes of microbial clearance and resistance and antibody formation to S. pneumoniae needs to be considered (21), particularly given recent data that marginal zone macrophages interact and retain B cells in this region (22). Here we show that marginal zone macrophages express a receptor called SIGN-R1 that is able to bind and internalize the capsular pneumococcal polysaccharide (CPS).…”

Mannose Receptor Ligand-Positive Cells Express the Metalloprotease Decysin in the B Cell Follicle

“…In the spleen, blood-borne Ags drain into the sinus of the marginal zone (MZ), 3 which surrounds the white pulp comprising the B cell follicle and the T cell-rich periarteriolar lymphoid sheath (PALS). The MZ contains the MZ macrophages that phagocytose Ag, and may play a role in presenting T cell-independent Ags to MZ B cells (1,2). Along the inner border of the MZ are located the MZ metallophils, also known as metallophilic macrophages, which are poorly phagocytic and express little MHC-II Ag (3).…”