Biomedical subjects

T Landsverk

Publications and source records attributed to T Landsverk.

At least 37 records · Page 2Linked to original sources

PubMed1997

Increase in gamma delta T cells in the ruminal mucosa of reindeer calves (Rangifer tarandus tarandus L.) induced by baled grass silage.

Leukocytes in the forestomach mucosa of reindeer (Rangifer tarandus tarandus L.) were investigated by immunoperoxidase staining of cryostat sections, using monoclonal antibodies against antigens on sheep leukocytes. Mucosal samples from three free-ranging reindeer calves were compared with samples from three calves fed baled grass silage previously shown to induce increased frequency of lesions in the ruminal epithelium. In both groups, MHC-II + cells and gamma delta T cells were observed, located within or just below the basal layer of the stratified epithelium. Computer-assisted morphometric analysis showed that the number of gamma delta T cells in the ruminal mucosa was higher in the silage-fed than in the free-ranging animals. No marked difference in number of MHC-II + Langerhans cells was observed between the groups.

Animals↗

PubMed1997

Apoptosis in phagocytotic cells of lymphoid tissues in rainbow trout (Oncorhynchus mykiss) following administration of clodronate liposomes.

Macrophage function has been studied in vivo by using liposomes that contain dichloromethylene-bisphosphonate (clodronate liposomes) to deplete macrophage subpopulations. In the present study, the effects of intravenously injected clodronate liposomes on the head kidney and spleen of the rainbow trout (Oncorhynchus mykiss) were studied from 1 h to 7 days after injection. The rapid trapping of liposomes in the splenic ellipsoids was followed by depletion of ellipsoidal sheath macrophages and accumulation of particulate material and IgM in the ellipsoidal wall, findings illustrating the importance of ellipsoidal macrophages in the clearance of filtered substances trapped in the reticular matrix of the ellipsoidal wall. A reduced reactivity for acid phosphatase in the spleen and ultrastructural evidence of cell death in phagocytotic cells of the head kidney and spleen supported the selective effect of clodronate liposomes on macrophages in rainbow trout. Apoptotic bodies were prominent ultrastructural features in tissues collected from clodronate-liposome-treated rainbow trout. The increased presence of apoptotic cells in clodronate-liposome-treated trout compared with trout given liposomes containing phosphate-buffered saline was confirmed by using terminal deoxynucleotidyl-transferase-mediated deoxyuridine-triphosphate nick-end-labelling of cells with extensive DNA fragmentation. The characterization of liposome-mediated macrophage depletion in fish provides a useful model for further investigation of piscine macrophage function.

Acid Phosphatase↗

PubMed1996

T cell subsets and Langerhans cells in the forestomach mucosa of adult sheep and sheep foetuses.

As part of a study on leukocytes in the ruminant forestomach the occurrence and distribution of T cells and major histocompatibility complex Class II positive (MHC-II+) cells in the forestomach mucosa of sheep were investigated. Samples were taken from the reticulum, atrium ruminis, ventral rumen, dorsal rumen and omasum of five healthy adult ewes and seven nearly fullborne foetuses. Frozen sections were stained with an indirect immunoperoxidase method using monoclonal antibodies against sheep MHC-II, CD4 and CD8 molecules and the sheep gamma delta T cell receptor. Both MHC-II+ cells and T cells were distributed along the basal lamina of the epithelium, with either mainly intraepithelial (CD8+ and gamma delta +cells) or mainly subepithelial (MHC-II+ and CD4+ cells) location. The MHC-II+ cells showed dendritic morphology and were interpreted as Langerhans cells. In adults ewes CD4+T cells comprised the major T cell subset at all sample sites. The number of T cells declined from the atrium ruminis through the ventral rumen to the dorsal rumen, while the number of Langerhans cells showed no marked variation between different sample sites. In foetuses, Langerhans cells showed a relatively high prevalence, while T cells were sparse and showed a more random distribution in the rumen wall. No marked variation between sample sites were observed in the fetal forestomachs. It is concluded that Langerhans cells and T cells are normally present in the forestomach mucosa of sheep, and it is suggested that the Langerhans cells represent a constituent component, while the prevalence and distribution of T cells may be influenced by antigen leakage through the epithelium.

Animals↗

PubMed1996

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

B-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 gamma delta T cells. The interfollicular areas of the PP of the markedly affected fetuses contained large populations of T cells. The spleen and lymph nodes were also markedly depleted of IgM+ cells and these tissues contained only a small, scattered population of weakly IgM+ cells. Follicular accumulations of IgM+ cells were absent. Large populations of T cells were present in the white pulp of the spleen and cortex of the lymph nodes. The liver did not contain IgM+ cells and the medulla of the thymus was depleted of IgM+ cells. The results of this study suggest that a surface IgM+ B-cell population is present in the sheep fetus at 63 days of gestation, which is essential for the colonization of the ileal PP and subsequent B-cell development.

Animals↗

PubMed1996

Response of leucocyte populations in the illeal Peyer's patch of fetal lambs treated with ferritin per os.

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.

Animals↗

PubMed1995

Nephrotoxicity of Narthecium ossifragum in cattle in Norway.

During the summer of 1992 renal failure was diagnosed in 232 grazing cattle in 85 herds on the west coast of Norway. The salient clinical signs were depression, anorexia and melaena or fresh blood in the faeces; diarrhoea was also commonly observed. The serum concentrations of creatinine, urea, magnesium and phosphorus, and the activities of glutamate dehydrogenase, aspartate aminotransferase and creatine kinase were above normal and the serum calcium concentration was below normal. Post mortem examinations consistently revealed renal tubular necrosis. In some cases there was liver necrosis and also erosions at the base of the tongue, in the oesophagus and in the jejunum and colon. The toxicity was probably caused by the plant Narthecium ossifragum (bog asphodel).

Animals↗

PubMed1995

Immune-complex trapping in the splenic ellipsoids of rainbow trout (Oncorhynchus mykiss).

Rainbow trout (Oncorhynchus mykiss), immunised with horseradish peroxidase, were given horseradish peroxidase intravenously, and the trapping of antigen in the spleen was followed 1, 24, and 48 h after injection. After 1 h, the localisation of horseradish peroxidase indicated that the antigen had been extensively trapped in the walls of the splenic ellipsoids. The colocalization of horseradish peroxidase with rainbow trout immunoglobulin M and complement factor 3 was shown with a double immunofluorescence technique and suggested that horseradish peroxidase was trapped in the form of immune complexes. After 24 and 48 h, very little horseradish peroxidase was detected in the ellipsoids, and horseradish peroxidase was mainly found in association with large cells with prominent cytoplasmic extensions. In non-immunized fish given horseradish peroxidase intravenously, antigen was not detected in ellipsoids. Thus, the observed difference between immunised and non-immunized trout suggests a specific role for the splenic ellipsoids in rapid immune-complex trapping and invites speculation on its significance in a secondary immune response.

Animals↗

PubMed1995

Spleen and kidney of Atlantic salmon (Salmo salar L.) show histochemical changes early in the course of experimentally induced infectious salmon anaemia (ISA).

Infectious salmon anaemia (ISA) is a disease of farmed Atlantic salmon (Salmo salar L.) in Norway that affects both erythrocytic and leucocytic cells. Both cell types are possible target cells for the aetiological ISA agent, which is probably a virus. In the present study the distribution and phenotype of leucocyte populations in the spleen and head kidney of Atlantic salmon that were developing ISA have been examined. Frozen tissues were collected from fish at various times after inoculation with ISA-infective material. Immune and enzyme histochemical techniques were used to characterise the response of leucocyte populations. Acid phosphatase positive macrophages predominantly in the red pulp of the spleen appeared to have engulfed erythrocytes at day 4 after infection. Evidence of degradation products of phagocytosed erythrocytes was present in macrophages in red pulp of the spleen at day 7 after infection, in addition to the usual site of erythrophagocytosis in melanomacrophage accumulations. Signs of erythrophagocytosis were not found in the head or body portions of the kidney. The activation of macrophages in the spleen at day 7 was suggested by decreased reactivity for the enzyme 5' nucleotidase. From day 7, clusters of immunoglobulin positive (Ig +) cells were present in the head kidney, while from day 11, the ellipsoids of the spleen showed reactivity for Ig and complement factor C3. These observations are discussed in relation to early immunoglobulin production and possible immune complex trapping. The present results suggest that the leucocyte populations in Atlantic salmon respond to ISA infection through macrophage activation and the initiation of an immune response.

Acid Phosphatase↗

PubMed1995

Scarcity of gamma delta T cells in intestinal epithelia containing coccidia despite general increase of epithelial lymphocytes.

Lymphocytes of intestinal epithelia were examined in lambs experimentally infected with coccidia. Fourteen conventional, coccidia-free 3-week-old lambs of the Dala breed were given either 250,000 (eight lambs in experiment 1) or 100,000 (six lambs in experiment 2) sporulated oocysts of Eimeria ovinoidalis (> 99.9% pure) via a stomach tube. Nine lambs (five in experiment 1 and four in experiment 2) of the same age served as uninoculated controls. The infected lambs developed diarrhea and dehydration between days 10 and 13 after infection. Intestinal specimens were collected 10-20 days after inoculation. A heavy multifocal infection of the epithelium comprising schizonts, gamonts, and oocysts resulted, with changes being most pronounced in the large intestine and the terminal part of ileum. Lesions included villous atrophy, villous fusions, and crypt hyperplasia. Computer-assisted morphometric analysis was applied to immunoperoxidase-stained sections for quantification of intraepithelial T cell subsets and included the distal jejunum of lambs of experiment 1. A significant increase in the epithelial area of the distal jejunum occupied by CD8+ lymphocytes was found in the infected lambs as compared with uninfected controls (18.3% versus 3.7%). The increased presence of CD8+ cells may be of significance in the intestinal immune response to ovine coccidiosis. A moderate, overall increase was also found for the gamma delta lymphocytes in the jejunal epithelium. Examination of the ileum of infected lambs of both experiments showed a scarcity of gamma delta cells (0.4% of epithelial area) in stretches of epithelium infected by coccida as compared with adjacent noninfected epithelium (4.0% of epithelial area).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Development and cell phenotypes in primary follicles of foetal sheep lymph nodes.

Lymph nodes from sheep foetuses and postnatal lambs were examined to determine the participation of different leucocyte populations in primary follicle formation, with special emphasis on the emergence and subsequent development of follicular dendritic cells during late gestation and early postnatal life. A series of immune and enzyme histochemical markers was used. The first 5'-nucleotidase-positive primary follicles were found at 80 days gestational age (gestation in sheep is 150 days) in superficial cervical lymph nodes. In the last month of gestation the primary follicles possessed follicular dendritic cells, macrophages, dendritic cells, and CD5-positive lymphocytes, in addition to IgM-positive cells. Follicular dendritic cells in primary follicles were found to be ultrastructurally immature. These follicular dendritic cells were characterised by a few, course surface projections and many ribosomes attached to the endoplasmic reticulum. A final differentiation to mature follicular dendritic cells was coincident with the postnatal germinal centre reaction. Computer-assisted morphometric analysis demonstrated that the size of 5'-nucleotidase-positive primary follicles in the distal jejunal lymph node, but not in the superficial cervical lymph node, increased significantly during late gestation. It was concluded that stromal cells in primary follicles of foetal sheep lymph nodes were a continuously developing population but that ultrastructural maturity was only achieved in the germinal centres of postnatal lambs.

5'-Nucleotidase↗

PubMed1994

Lymphoid follicles in the gastric mucosa of dogs. Distribution and lymphocyte phenotypes.

The occurrence and distribution of lymphoid follicles within the stomachs of 36 dogs that did not have macroscopic gastric lesions are presented. The dogs ranged in age from less than 1 year to over 13 years. The number of follicles varied between the different regions of the stomach, being most numerous (15.6 follicles cm-2) and uniform in size (about 1 mm in diameter) in the fundus. The number and size of follicles in the antrum varied widely between dogs. Age-related changes in the distribution of follicles were not found following simple linear regression analysis. The phenotypes of lymphocytes in gastric lymphoid follicles of nine dogs aged from less than 1 year to 5 years were determined using monoclonal antibodies specific for canine leucocyte antigens and an indirect immunoperoxidase technique. The follicles had an organized distribution of lymphocytes subsets in that a predominantly B cell area contained some CD4+ cells and very few CD8+ cells and was adjacent to an area containing mostly T cells. Computer-assisted morphometric analysis was used to quantify the overall presence of the various lymphocyte subpopulations. Follicles in the fundus and body regions possessed similar percentages of lymphocytes averaging 42%, 22% and 3% of the area occupied by B cells, CD4+ and CD8+ cells, respectively. It is concluded that lymphoid follicles are a normal constituent of the canine gastric mucosa and possess a lymphocyte composition similar to that reported by others for solitary intestinal follicles.

Animals↗

PubMed1994

Lymphocyte subpopulations in jejunal and ileal Peyer's patches of calves with experimental Salmonella dublin infection.

Changes of lymphocyte subpopulations in jejunal and ileal Peyer's patches (JPP and IPP) of six calves inoculated with Salmonella dublin were investigated at 9 hours, 1, 2, 3 and 7 days post inoculation (p.i.) using immunohistochemistry. Reactive areas and area percentages of B-lymphocytes, as well as CD4+, CD8+ and gamma delta T-lymphocytes within the different compartments of PP were estimated using computer-assisted morphometric analysis. A significant, linear decline of the areas of lymphoid follicles and domes in JPP and IPP due to depletion of B-lymphocytes was found. The rate of decline was similar in JPP and IPP, but more severe in lymphoid follicles than in domes. Intraepithelial cells in follicle-associated epithelium changed from predominantly B-lymphocytes in controls to CD8+ T-lymphocytes in inoculated calves and clusters of B-lymphocytes were observed above domes at days 1 and 2 p.i. Areas of CD4+ and CD8+ T-lymphocytes within lymphoid follicles and domes were increased at 3 and 7 days. p.i. resulting in decreased compartmentalization of the normally segregated T- and B-lymphocyte populations. The increase of CD4+ and CD8+ T-lymphocytes was, however, significant in lymphoid follicles in the JPP only. No significant changes in the amount and distribution of gamma delta T-lymphocytes were observed.

Animals↗

PubMed1994

Gastropathies in the Lundehund. II. A study of mucin profiles.

The mucin profiles of the gastric mucosa in Lundehunds suffering from intestinal lymphangiectasia were examined and compared to the mucin profiles in control dogs from other breeds. A previous study performed on this material had shown that all examined Lundehunds had gastritis and about 30% had gastric carcinoma. Neutral and acid mucins were identified using the periodic acid-Schiff (PAS) and Alcian blue (pH 2.5) periodic acid-Schiff (AB-PAS) methods. The acid mucins were divided into sialomucins and sulfomucins based on their reaction with high-iron diamine Alcian blue, pH 2.5 (HID-AB). In Lundehunds with chronic atrophic gastritis in the fundic and body regions the surface and foveolar epithelium showed a predominantly normal mucin profile although some Lundehunds had a reduced mucin content. The mucous neck cells extended from below the gastric foveolae towards the muscularis mucosae. Morphometric examination showed that the abnormal presence of mucous neck cells occupied 41% of the height of the gastric mucosa in Lundehunds compared to only 19% in the control dogs (p < 0.05). Of the four Lundehunds with gastric carcinoma, two possessed neoplastic cells that contained minimal or no mucins. The amount and type of mucin in the neoplastic cells of the remaining two Lundehunds varied both between individuals and within a neoplasm. This study shows that the abnormal presence of mucous neck cells and the associated pseudopyloric metaplasia comprised the predominant changes in the gastric mucin profiles of Lundehunds.

Animals↗

PubMed1994

Gastropathies in the Lundehund. I. Gastritis and gastric neoplasia associated with intestinal lymphangiectasia.

The results from gross and microscopic examination of the stomachs of Lundehunds and examination of stomachs of control dogs from other breeds were compared. Over a 13-year period, 12 of 14 autopsied Lundehunds have been diagnosed as having intestinal lymphangiectasia. In the present study, histological examination revealed gastritis as manifested by an increase in the number of mononuclear cells infiltrating the lamina propria in all the Lundehunds. The inflammation was chronic and restricted to the fundic and body regions, except in one Lundehund where antral gastritis was also present. Computer-assisted morphometric analysis was used to quantify the increased number of mononuclear cells. Atrophy of mucosal fundic glands was prominent in most Lundehunds and mucous metaplasia was often present. Conventional morphometry revealed a significant decrease in the height of the gastric mucosa. A relative expansion in area of the basal part of the lamina propria in Lundehunds with chronic atrophic gastritis corresponded to the observed increase in mononuclear cells and stromal elements. Primary gastric carcinoma with neoplastic cells infiltrating layers of the stomach wall was found in four Lundehunds. The high incidence of gastric carcinoma and the consistent presence of gastritis in Lundehunds suffering from intestinal lymphangiectasia suggest that these changes represent features of a single pathogenetic process.

Animals↗

PubMed1993

Potassium-dependent p-nitrophenyl phosphatase and carbonic anhydrase reactivities suggest that lymphoid follicles in the large intestine of lambs are lined with a uniform type of epithelial cell distinct from the absorptive epithelium.

The epithelium covering the large intestinal lymphoid follicles in fetal and postnatal lambs was examined for potassium-dependent p-nitrophenyl-phosphatase (K(+)-NPPase), carbonic anhydrase, magnesium-dependent adenosine triphosphatase (Mg(2+)-ATPase) and acid phosphatase. Reactivities for these enzymes indicated a homogenous population of cells in the follicle-associated epithelium (FAE), distinct from the absorptive epithelium. There were essentially no differences in the enzyme reactivities of the large intestinal FAE between fetuses in late gestation and postnatal lambs. The FAE showed a weak reaction for K(+)-NPPase and a variable staining for Mg(2+)-ATPase and acid phosphatase. In contrast, the adjacent absorptive epithelium demonstrated strong reactions for these enzymes. Carbonic anhydrase gave a strong reaction at the luminal and apparent basolateral cell borders of the large intestinal FAE. This distribution of reactivity for carbonic anhydrase resembled that found in the ileal FAE. In absorptive epithelial cells, only the luminal cell border reacted strongly for carbonic anhydrase. Serial sections of large intestinal tissue showed a variation in the basolateral staining of FAE from one section to the next, a finding which suggested that the reaction may be associated with transcytosis. The lymphoid follicles and domes of the large intestine showed a variable granular pattern of carbonic anhydrase staining, which also suggested a dependence on epithelial transcytosis.

4-Nitrophenylphosphatase↗

PubMed1993

Enzyme changes in remodelling epithelial cells: a histochemical study of the rat jejunum in vivo during and following exposure to deoxycholic acid.

Loops of rat jejunum were exposed in vivo to different concentrations of deoxycholic acid (DOC; 0, 2.5, 5, 10 and 20 mM). Following a 30 min exposure period, DOC was washed out of the loops and the intestines were allowed to recover for 15 or 150 min. Frozen tissue for enzyme histochemistry was collected during exposure and following the recovery periods. As shown previously, exposure to DOC caused a dose-dependent loss of epithelial cells at the villous tips and denudation of the lamina propria. Flattened epithelial cells bordering the denuded areas were, however, responsible for a rapid restoration of epithelial continuity, which was completed within 15 min. In the present study, these flattened cells showed normal reactivity for non-specific esterase and succinate dehydrogenase. In contrast, following a prolonged recovery period (150 min), a subpopulation of enterocytes at the villous tips that otherwise appeared normal showed decreased reactivity for brush border enzymes and non-specific esterase, and a positive reaction for mucin. A shutdown in the synthesis of cytoplasmic enzymes and redistribution of cell surface enzymes could be responsible for these late occurring enzyme changes, that were consistently observed after 150 min of recovery from DOC at 20 mM. Alternatively, retention of goblet cells and/or a modification in enzyme synthesis may explain the presence of mucin that was demonstrated in the epithelial cells which had low enzyme reactivity.

Alkaline Phosphatase↗

PubMed1993

Atrial natriuretic factor (ANF) does not affect ion transport in human intestine but does in porcine intestine.

The aim of this study was to test whether atrial natriuretic factor (ANF) exerts any effect on human intestinal ion transport, and the porcine intestine was used as a positive control of ANF's effects. Tissues from human proximal (n = 6) and distal (n = 6) colons, and from distal ileum (n = 6) were mounted in Ussing chambers, and short circuit current (Isc) was measured subsequent to serosal application of ANF (10(-6) M), 8-Br-cyclic guanosine monophosphate (8-Br-cGMP) (10(-4) M), and theophylline (10(-2) M). ANF did not affect Isc whereas 8-Br-cGMP increased Isc by 28 (8-53), 16 (3-36), and 16 (5-41) microA cm-2 in the distal colon (DC), proximal colon (PC) and distal ileum (DI), respectively. Likewise, transepithelial potential difference (PD) became more negative by 5.0 (0.6-8.9), 2.5 (0.4-4.0) and 0.9 (0.3-2.3) mV in DC, PC, and DI, respectively, subsequent to addition of 8-Br-cGMP. Isc and PD were further increased by theophylline. Additional radio-isotope flux studies in human colon revealed that ANF did not affect electroneutral sodium and chloride transport either. For comparison, ANF (10(-6) M) was administered to large intestinal tissues from young pigs in which ANF induced a significant increase in Isc which was comparable to the 8-Br-cGMP response in humans. The porcine Isc response was partly inhibited by chloride-free solution on the serosal side, by serosal application of bumetanide (10(-4) M) and BaCl2 (10(-3) M), and mucosal application of the chloride-channel blocker diphenylamine-2-carboxylate (DPC) (10(-3) M). Mucosal amiloride (10(-5) M) pre-treatment reduced baseline Isc but did not affect the porcine intestinal Isc response to ANF. In vitro radio-autography demonstrated specific binding sites for ANF in porcine distal colon, whereas no apparent labelling was observed in human distal colon. These findings suggest that the lack of effect of ANF on sodium and chloride transport in human distal ileum and colon is probably due to lack of ANF receptors. In the porcine intestine, however, the Isc response induced by ANF seems to involve stimulation of electrogenic chloride secretion, whereas electrogenic sodium absorption seems unaffected.

Adolescent↗

PubMed1993

Ontogeny of leucocyte populations in the spleen of fetal lambs with emphasis on the early prominence of B cells.

The presence and distribution of B cells and other early leucocyte populations are described in the spleen of fetal lambs from 40 to 134 days of gestation (length of gestation 150 days). Computer-assisted morphometric analysis and flow cytometry were used to quantify the early predominance of B cells in mid-gestation. B cells appeared at about 48 days and increased in number to occupy over 20% of the spleen area at 77 days. All spleens were collected on their respective livers and at no stage did the livers contain more than a few IgM-positive (+) cells, which were usually close to blood vessels. Two-colour flow cytometry demonstrated that only 1-2% of IgM+ cells expressed CD5 at 81 days. Beyond 77 days, with the expanding presence of T cells, the percentage of area occupied by IgM+ cells declined to stabilize at about 7% during late gestation. The conventional organization of the splenic white pulp was observed from 90 days along with 5' nucleotidase-positive primary follicles. Double staining technique using immunohistochemical methods demonstrated that IgM+ cells were proliferating in the spleen from as early as 51 days and that clusters of proliferating IgM+ cells were prominent between 60 and 77 days. The results of the present study suggest that during the ontogeny of fetal lambs the spleen is a site of B-cell development or expansion before colonization of the ileal Peyer's patch and the subsequent generation of the preimmune antibody repertoire.

Animals↗