Fetal lambs are depleted of IgM⁺ cells following a single injection of an anti‐IgM antibody early in gestation

Abstract

SUMMARYB-cell depleted fetal sheep were created following a single injection of an anti-IgM monoclonal antibody early in gestation. Six sheep fetuses were given a single intraperitoneal injection of a monoclonal antibody directed against IgM at 63 days of gestation (gestation in sheep 150 days). The fetuses were killed at 138-142 days of gestation and lymphoid tissues were collected for subsequent light microscopy and immunohistochemical examination. The ileal and jejunal Peyer's patch (PP) follicles in four of the six injected fetuses were markedly reduced in size. Cells in the rudimentary follicles of the ileal PP of these animals showed no reactivity for IgM and most were negative for CD45. The dome regions contained many T cells, which were predominantly CD8 cells and included

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

“…The marginal zone is an important B-cell compartment in the spleen . The spleen of B-cell-depleted fetal lambs, which lack the strongly IgM marginal zone B cells Press et al, 1996), also lacked the strongly nonspecific esterase-positive marginal metallophilic macrophages, although some weakly nonspecific esterase-positive, acid phosphatase-positive marginal-zone macrophages did appear to be present. In mice, four subpopulations of splenic macrophages, namely, red pulp macrophages, white pulp macrophages, marginal-zone macrophages, and marginal metallophilic macrophages, have been recognized on the basis of differences in localization, membrane antigens, and repopulation kinetics after depletion (Dijkstra et al, 1985;Van Rooijen et al, 1989).…”

“…In mice, four subpopulations of splenic macrophages, namely, red pulp macrophages, white pulp macrophages, marginal-zone macrophages, and marginal metallophilic macrophages, have been recognized on the basis of differences in localization, membrane antigens, and repopulation kinetics after depletion (Dijkstra et al, 1985;Van Rooijen et al, 1989). The marginal metallophilic macrophages and marginal-zone macrophages have been shown to perform different roles in mounting humoral immune responses (Buiting et al, 1996) (Press et al, 1996). An understanding of the significance of these leucocyte populations will probably depend on the further characterisation of B-cell-depleted fetal sheep and the mechanism(s) involved in the maintenance of B-cell depletion following a single treatment with an anti-IgM antibody early in gestation.…”

“…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.…”

“…However, differences were observed between stromal-cell populations in the spleen and lymph nodes and stromal cells in the ileal Peyer's patch. A previous study has shown that the ileal Peyer's patch of B-cell-depleted fetal sheep did not contain B cells and only a small, scattered population of B cells was present in the spleen and lymph nodes (Press et al, 1996). With the depletion of B cells, conventional secondary lymphoid tissues of the spleen and lymph nodes did not show typical patterns of enzyme reactivity for FDCs in primary follicles, whereas the FDCs in the ileal Peyer's patch continued to express strong reactivity for 5'N (Halleraker et al, 1990;1994;Nicander et al, 1991).…”

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

“…Ig Vλ gene diversity is also found in fetal cattle spleen but not in the liver, ileum, or blood during the pre-PP phase of development [63]. It has been shown in the 56 days old fetal lamb that a single injection of antiIgM antibody will cause the failure of development of lymphoid follicles in PP; however, splenectomy at the same fetal age did not prevent PP formation [91,93]. These studies provided evidence that B-cells do not continually enter the rudimentary PP follicles.…”