In vitro complement-dependent binding and in vivo kinetics of pneumococcal polysaccharide TI-2 antigens in the rat spleen marginal zone and follicle

Abstract

For a better understanding of the spleen-dependent induction of the humoral immune response against thymus-independent type 2 antigens, we have studied the in vitro and in vivo localization of different capsular pneumococcal polysaccharides (PPSs) in the rat spleen. In this study, we found that in vitro binding of PPS types 3, 4, 6B, 9N/V, 14, and 23F was dependent on complement (probably a C3 fragment) and that the localization was predominantly restricted to the marginal-zone B lymphocytes and the follicular dendritic cells. In vivo, we observed with increase of time a shift of localized antigens. Shortly after injection, all PPS types localized in the marginal-zone B lymphocytes, then localized in the outer follicular mantle, and finally were found to be diffuse in the complete follicle and follicle corona. PPS types 3 and 9N/V and later also PPS type 23F localized additionally in red pulp macrophages. In particular, the localization in the marginal zone is important since the low flow in this area in combination with strongly CD21 ؉ B cells, which are activated early, gives a maximum opportunity for the induction of a primary humoral immune response with subsequent differentiation into plasma cells or migration to the germinal center. In addition, the localization of PPSs at follicular dendritic cells should be considered important in the induction of an ongoing immune response not restricted to the spleen.

After chemotherapy, functional humoral response capacity is restored before complete restoration of lymphoid compartments

“…Five days after injections it can be traced in the germinal centres showing a typical FDC associated staining pattern ( Fig. 3) [11]. Rats treated with CP or MTX 2 days before vaccination with PPS showed a same localization pattern as observed in control rats (Table 1).…”

“…Previously, we have demonstrated that polysaccharides rapidly localize specifically on the splenic marginal zone B cells and not the marginal zone macrophages by immunohistological (double staining) examination of spleens of rats injected with polysaccharides [11]. Within 24 h, PPS shifts to the follicles and at 5 days after vaccination the polysaccharides can be traced in the secondary follicles bound in a FDC like fashion [11]. When injecting polysaccharides 2 days after chemotherapy, we still found localization of polysaccharides within 15 min in the marginal zone.…”

“…In the marginal zone this requirement is fulfilled because of the low blood flow and high expression of complement receptor 2 (CR2, CD21) on marginal zone B cells [6,7]. Marginal zone B cells are particular well-suited for a rapid humoral immune response to blood-borne antigens in general but specifically to antigens derived from encapsulated bacteria [8][9][10][11][12], bacteria that pose a problem during chemotherapy.…”

The dual function of the splenic marginal zone: essential for initiation of anti-TI-2 responses but also vital in the general first-line defense against blood-borne antigens

“…A functional spleen is essential for the immune response to TI-2 antigens [3,10,13]. Absence or dysfunction of the spleen results in an increased risk of infections caused by bacteria that have a polysaccharide capsule [17][18][19].…”

“…The second function of the S-MZ is a more unique one and involves the initiation of an immune response to T cell indepen-dent type 2 (TI-2) antigens [3][4][5][10][11][12]. Based on immunogenicity in congenitally athymic ( nu/nu ) mice and mice with and X-linked immune B cell defect ( xid-mice), antigens are divided in T-cell dependent (TD), T-cell independent type 1 (TI-1) and T-cell independent type 2 (TI-2) antigens.…”