Response of Leucocyte Populations in the Ileal Peyer's Patch of Fetal Lambs Treated with Ferritin Per Os

Journal of Immunology Research, Aug 2018

A combination of immunohistochemical techniques, a panel of monoclonal antibodies, and computer-assisted morphometric analysis was used to examine the response of the ileal Peyerr's patch of fetal lambs 7 days after treatment with ferritin per os. Consistent with previous studies in fetal lambs that have reported the ileal Peyer's patch to be indifferent to antigen, the present study did not find any significant changes in the size of the predominantly B-cell dome/follicle compartment or the predominantly T-cell interfollicular area, nor were differences identified in the distribution of IgM-positive (

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Response of Leucocyte Populations in the Ileal Peyer's Patch of Fetal Lambs Treated with Ferritin Per Os

Response of Leucocyte Populations in the Ileal Peyer's Patch of Fetal Lambs Treated with Ferritin Per Os LENA H.M. RENSTROM CHARLES McL. PRESS " WENDY TREVELLA THOR LANDSVERK A combination of immunohistochemical techniques, a panel of monoclonal antibodies, and computer-assisted morphometric analysis was used to examine the response of the ileal Peyer's patch of fetal lambs 7 days after treatment with ferritin per os. Consistent with previous studies in fetal lambs that have reported the ileal Peyer's patch to be indifferent to antigen, the present study did not find any significant changes in the size of the predominantly B-cell dome/follicle compartment or the predominantly T-cell interfollicular area, nor were differences identified in the distribution of IgM-positive (+), CD4 +, and CD8+ cells in these two compartments. However, both compartments showed a significant increase (p < 0.05) in the percentage of area occupied by MHC II + cells and a significant decrease (p < 0.05) in the percentage of area occupied by CD44+ and B5+ cells. These changes show that the ileal Peyer's patch of fetal lambs is not indifferent to antigen and may represent the transition of a purely primary lymphoid organ to an organ that has both primary and secondary lymphoid functions. Fetal sheep; ferritin; leucocytes; activation; MHC II; computer-assisted morphometric analysis INTRODUCTION In sheep, the ileal Peyer?s patch (PP) produces the vast majority of circulating B cells (Gerber et al., 1986) and is responsible for the generation of the preimmune antibody repertoire (Reynaud et al., 1991) . Active lymphopoiesis is present in PP from about 110 days of gestation (length of gestation in sheep is 150 days) (Reynolds and Morris, 1983) and occurs in the absence of exogenous nonself antigens. The sheep fetus is shielded from maternal immunoglobulins and even small molecules by a syndesmochorial placenta (Brambell, 1970; Boyd et al., 1976) . The introduction of foreign substances into this protected environment has shown that the fetal lamb can mount an immune response to many antigens including ovalbumin, ferritin, and killed Brucella abortus organisms (Silverstein et al., 1963; Fahey and Morris, 1974, 1978) . Although clear evidence of histological changes was present in the Corresponding author. mesenteric lymph nodes and lamina propria of the intestine of fetal lambs following exposure to an antigen such as ferritin (Husband and McDowell, 1975; Reynolds and Morris, 1984) , changes in ileal PP histology were not detected (Reynolds and Morris, 1984). The ileal PP was considered indifferent to foreign antigen, and this was argued as further support for the antigen independence of lymphopoiesis in this organ (Reynolds and Morris, 1984) . Recent studies of somatic hypermutation of light-chain V genes in the ileal PP of fetuses and lambs have shown that the hypermutation process is also independent of the presence of external antigens (Reynaud et al., 1995) . However, the rate of B-cell proliferation following the introduction of foreign antigen or indeed the hypermutation process generating the repertoire does not describe the resultant antibody repertoire. Active lymphopoiesis in the ileal PP is accompanied by massive cell death and it is estimated that only 5% of PP cells produced there are destined to leave their site of production (Reynolds, 1986; Motyka and Reynolds, 1991) . Thus, intense selection occurs in the PP that shapes the preimmune antibody the mean interfollicular area in the control group was 9102.24+ 1871.39 xm2 compared with 5956.52+608.11 gm2 in the ferritin-treated group; not significant) (Fig. 3). The mean percentages of area occupied by the leucocyte subpopulations identified by staining for IgM, CD4, and CD8 in the two compartments were also not significantly different when comparing the ferritin-treated and control groups of fetal lambs (Fig. 4). The percentage of areas occupied by T-cell subpopulations showed a tendency to increase in the dome/follicle and to decrease in the interfollicular area. The most marked decrease in T-cell subpopulations was in the percentage of area occupied by the CD4 + cell population in the interfollicular area (21.07+8.27% in the control group compared with 5.70+2.00% in the ferritin-treated group; not significant). Despite the widely different percentages of areas occupied by IgM + cells in the two lymphoid compartments of the ileal PP, both percentages decreased in ferritin-treated lambs (dome/follicle control 62.73 + 7.00% compared with ferritin-treated 43.70+ 13.63%; interfollicular area control 7.54 + 2.92% compared with ferritin-treated 3.83 + 1.26%; both not significant). There was a significant increase in the mean percentage of the area staining for MHC II in both the dome/follicle (control 34.85+7.14% and AREA 10 o00 < < < lOO 80 60 40 20 50 40 30 20 10 50 40 30 20 10 IgM D/F Ferritin IF C D 4 D/F IF Control D/F Ferritin IF D/F C (...truncated)


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Lena H. M. Renström, Charles Mcl. Press, Wendy Trevella, Thor Landsverk. Response of Leucocyte Populations in the Ileal Peyer's Patch of Fetal Lambs Treated with Ferritin Per Os, Journal of Immunology Research, 4, DOI: 10.1155/1995/96934