Development of Accessory Cells in B‐Cell Compartments Is Retarted in B‐Cell‐Depleted Fetal Sheep

Abstract

(Halleraker et al., 1994). As sheep are only exposed to exogenous nonself antigens after birth because of the protection provided by a syndesmochorial placenta (Brambell, 1970;Boyd et al., 1976), it follows that factors other than exogenous nonself antigens are responsible for this modification.The interdependence of lymphoid-cell differentiation and stromal-cell development has been the subject of a number of studies. In man, rat and sheep, the early occurrence of FDCs was concomitant with B-cell aggregation and the appearance of primary follicles (Markgraf et al., 1982;Kroese et al., 1987;Halleraker et al., 1994 (Press et al., 1996) has allowed the investigation of the development of lymphoid and accessory-cell populations in a species shielded from exogenous antigen during gestation. In addition to FDCs in primary follicles, other accessory-cell populations that share a close association with B cells include the FDCs of gut-associated lymphoid follicles and macrophages of the marginal zone of the spleen. The aim of the present study was to characterize, using a panel of enzyme and immunohistochemical techniques, the accessory-cell populations in the lymphoid tissues of B-cell-depleted fetal sheep. RESULTS Ileal Peyer's Patch FolliclesThe small follicles in the ileal Peyer's patch of the Bcell-depleted fetuses demonstrated intense reactivity for the enzyme 5'nucleotidase (5'N), which was similar to the intensity of reactivity shown in the ileal Peyer's patch follicles of the untreated litter mates and the age-matched control fetuses (Figure 1). There was intense reactivity for magnesium-dependent adenosine triphosphatase (MgATPase) in some cells of the dome and interfollicular areas in the ileal Peyer's patch of the B-cell-depleted fetuses ( Figure 1). The dome region of ileal Peyer's patch of the Bcell-depleted fetuses showed increased reactivity for acid phosphatase whereas there was an absence of reactivity in the rudimentary follicle (Figure 1) There was also some reactivity for nonspecific esterase in the dome and interfollicular areas (not shown).A double immunofluorescence technique showed that the rudimentary follicles of the ileal Peyer' s patch in the B-cell-depleted fetuses showed strong staining for complement receptor-2 (CD21) and did not stain for IgM (not shown). Primary Follicles in the Spleen and Lymph NodesThe spleen and lymph nodes of the B-cell-depleted fetuses did not show the characteristic patterns of enzyme reactivity for 5'N, MgATPase, nonspecific esterase, and alkaline phosphatase that are associated with primary follicles (Figure 1). Serial step sectioning of the spleen and lymph nodes combined with staining for 5'N reactivity did not identify primary follicles in the B-cell-depleted fetuses. Primary follicles were readily identifiable by their typical pattern of enzyme reactivities in the control fetuses (Figure 1).The spleen and lymph nodes of B-cell-depleted fetuses contained a small population of CD21 cells.In the lymph nodes, most of these cells were scattered in the cortex, b...

The sheep and cattle Peyer’s patch as a site of B-cell development

“…Follicular dendritic cells that are reactive with 5' nucleotidase and Mg 2+ dependent adenosine triphosphatase are also seen in the ileal PP as well as in other primary lymphoid follicles in peripheral lymph nodes [43,75]. Depletion of Bcells from fetal lambs by anti IgM antibody injection generated PP follicles composed of clusters of FDC's [60,92]. Ileal PP follicles have also been used to generate a number of clones of mesenchymallyderived stromal cells [38,39].…”

“…The analysis of other accessory cells found in the ileal PP follicles has involved the use of the B-cell depleted fetal lambs described above [42,60,89,92]. The rudimentary follicles of ileal PP in these animals show strong reactivity for 5' nucleotidase, indicating the presence of follicular dendritic cells.…”

“…The rudimentary follicles of ileal PP in these animals show strong reactivity for 5' nucleotidase, indicating the presence of follicular dendritic cells. Mg-ATPase + dendritic cells are present at an early developmental stage [89] as are macrophages that stain with non-specific esterase and acid phosphatase [42,92]. The sheep ileal PP follicle also contains many tingible-body macrophages whose role it is to rapidly eliminate apoptotic cells [13].…”

Differentiation of the follicle-associated epithelium in ileal Peyer?s patch and production of 50-nm particles are maintained in B-cell-depleted fetal sheep

“…Previous investigations of B-cell-depleted fetal sheep have shown that the dome areas in these animals contain both CD4+ and CD8+ cells, which might be involved in the formation of FAE (Press et al 1996(Press et al , 1998. However in other species, these cell types seem to have a limited role.…”

The Effect of Dosage, Gestational Age and Splenectomy on Anti‐IgM Interception of Prenatal B‐cell Development in Sheep

“…If, as other findings in this study suggest, the effect of anti-IgM administration is related to the concentration of mouse immunoglobulin in serum, then the effect of administration of antibody at 56 dg can at most have been present until 77 dg. The investigation of B-cell depleted foetal sheep has shown that rudimentary follicles containing follicular dendritic cells are present in the ileum just prior to birth (Press et al, 1998) and that B-cell populations, albeit reduced, are present in the spleen, lymph nodes and jejunal Peyer's patch (Press et al, 1996). The question is then why in the absence of anti-IgM antibody, do the B-cell populations that are present in B-cell depleted foetal lambs fail to colonise the emerging lymphoid nodules of the ileal Peyer's patch in the remaining 73 days of gestation?…”