On the development of the lymphoid follicles of the bursa of fabricius

The structural features of the development of the bursa of Fabricius in white Leghom chick embryos are depicted at carefully timed intervals during embryogenesis, with emphasis on the sequence of events between the ninth and twelfth days of incubation. The direction and character of the migration of lymphoid cell precursors and granulocytes from the intravascular space to intraepithelial sites, where the formation of the primitive lymphoepithelial nodule takes place, is demonstrated. The mechanism of the mode of migration of these cells through the stromal epithelial interface is described and illustrated with electron micrographs and their role in the development of the primitive lymphoid follicles is described and discussed.     

Immunoglobulin- and J chain-producing cells associated with lymphoid follicles in the human appendix, colon and ileum, including Peyer''s patches.

Immunohistochemistry of B cells associated with normal human Peyer's patches and solitary lymphoid follicles of the ileum, colon and appendix mucosa showed that local accumulation of IgG-producing cells is a common feature of gut-associated lymphoid tissue (GALT). These immunocytes have strikingly down-regulated J-chain expression, indicating that they belong to mature memory clones. They are located mainly in the dome areas, alongside the follicles, and to a lesser extent in the germinal centres, and are accompanied by a much smaller number of J-chain negative IgA- and IgM-producing cells. It is concluded that B cells of mature memory clones are retained in GALT, whereas relatively early counterparts with a high J chain-expressing potential probably emigrate rapidly after stimulation and seed distant secretory sites where they undergo terminal differentiation to produce mainly J chain-containing dimeric IgA.     

Peyer's patches in experimental Salmonella dublin infection in calves. Microvascular and epithelial changes contributing to atrophy of lymphoid follicles.

Six calves were infected per os with Salmonella dublin and killed nine hours to seven days later. Early changes included occlusion of capillaries with a hyaline material, particularly in the ileal Peyer's patch (PP). Central areas of the follicles contained hemorrhages and edema. In later stages the follicle-associated epithelium (FAE) of both the jejunal and ileal PP was fused with the adjacent epithelium and the follicles were collapsed. As judged from 5'nucleotidase histochemistry, follicles were depleted of lymphocytes whereas reticular cells were retained. Carbonic anhydrase (CA) histochemistry showed a decreased reaction in the ileal FAE and a reduced amount of CA reactive material in the follicles of the ileal PP, indicating loss of FAE differentiation and function. Hyaline material and fibrinous thrombi were seen occluding the blood capillaries and the lymphatics, respectively. The villi were atrophied and covered with thick fibrin deposits. Using antifibrinogen antibodies, immunoperoxidase stained fibrin in the lymphatics and the lumenal deposits but not the hyaline material in the capillaries. Reaction for CA indicated that this hyaline material originated from erythrocytes. Factors contributing to the follicle atrophy may include anoxia due to stasis in the microcirculation with the formation of erythrocyte thrombi, and reduced lymphopoiesis due to a decrease in the stimulating factors provided by the FAE.     

T-dependent areas in the chicken bursa of fabricius: An immunohistological study

Background: The so-called diffusely infiltrated lymphoid tissue of the chicken bursa of Fabricius was previously described as a T-dependent bursal area. Methods: We have analyzed immunohistologically its postnatal development by using a battery of mAbs, most of them raised specifically to chicken T cells, in order to characterize phenotypically the nature of its cell components, appearance, development, and possible functional significance. Results: Our results demonstrate that this tissue represents poorly developed lymphoid aggregates, the cell content reminiscent of that found in other lymphoid tissues occurring throughout the avian gut. The first lymphoid elements appear in this bursal area only after hatchin, growing rapidly to reach the adult condition in the second week of postnatal life. They consist mainly of T lymphocytes, including principally CD4⁺ TcRαVβ1⁺ cells, which form cell groups and CD8⁺ cells, and TcRγδ⁺ lymphocytes, which predominate in the subepithelial area and within the epithelium. MHC Class II molecule-expressing cells and IgM-, IgG-, and IgA-positive B lymphocytes also occupy the subepithelial region. Conclusions: We propose that the bursal diffusely infiltrated lymphoid tissue of the chicken represents gut-associated lymphoid tissue involved in mounting immune responses to antigens that reach the bursal lumen via the cloaca. © 1995 Wiley-Liss, Inc.     

Dome epithelium and follicle-associated basal lamina pores in the avian bursa of fabricius

Background: The immunological role played by the avian bursa of Fabricius has been well established. Although numerous studies have also reported on the development and general morphology of this organ, some structure-function relationships still hae not been fully explained. Methods. Bursae from chickens at three developmental stages were removed and examined by scanning electron micropscopy. Routine preparation was used as well as sonication (Microdissection). Micrographs were used for qualitative morphological study and for quantitative morphometric analyses. Results: Routine SEM observations were similar to those previously reported in the literature. Sonicated specimens allowed topographical study of various levels of surface erosion. Two types of surface cells were observed: typical absorptive epithelium and follicle-associated epithelial (FAE) cells. Erosion of the dome surface epithelium revealed basal lamina pores n the region over the subepithelial lymphoid follicles. These pores were present at hatching. Morphometric analysis of dome and pore areas. Conclusions: Basal lamina pores may provide a communication route between the lympghoid follicles and the external environment via the FAE cells. Also, the close association between the FAE cells of the epithelial domes, the epithelial pores, the capillary complex of the previously described bursal-blood barrier, and the subepithelial lymphoid follicles could represent a morphological “pure complex” that matures early in posthatching development and may be related to the immunological function of the bursa. © 1995 Wiley-Liss, Inc.     

Follicle-associated epithelium and medullary epithelial tissue of the bursa of fabricius are two different compartments.

The bursae of Fabricius from the chicken and turkey were studied by light and electron microscopy and immunohistochemical methods. The study focused on the relationship of follicle-associated epithelium to the medulla. The follicle-associated epithelium was supported by 3 to 5 layers of stratified epithelial cells which were a continuation of the corticomedullary epithelial cells. The follicle-associated epithelium consisted of M cells and scattered secretory dendritic cells. The network of the reticular epithelial cells of the medulla was filled with secretory dendritic cells, B cells, and a few T cells and macrophages. The cellular content of the follicle-associated epithelium and the medulla suggested that they were different cellular compartments. Communication between the follicle associated epithelium and medullary epithelial compartment occurred through the supporting cells of the follicle-associated epithelium. When the supporting layers of the follicle-associated epithelium infolded into the medulla, they formed lamellated epithelial bodies similar to the thymic Hassall bodies. The lamellated bodies enclosed secretory dendritic cells but not lymphocytes. The infolding of supporting cells varied from follicle to follicle. The asynchronization of infolding contributed to heterogeneity of follicle composition. Follicle heterogeneity was demonstrated by differences in reactivity with a battery of monoclonal antibodies.     

An electron microscopic study of esophageal epithelium in the newborn and adult mouse

The stratified squamous epithelium of the esophagus in the newborn and adult mouse was studied by histological, histochemical and electron microscopic methods. In the newborn, the cells located above the basal layer elaborate mucus. The relative abundance of Golgi zones and rough-surfaced endoplasmic reticulum suggests the involvement of these organelles in the production of mucous granules. The membrane of mature mucous granules ruptures and their contents become dispersed in the cytoplasm. Mature mucous granules are not seen in the outermost cells which are about to be exfoliated. The process of exfoliation begins in the upper layer of the epithelium when the contiguous cell membranes separate and wide intercellular spaces are formed. While the cells reach the surface, the intercellular spaces widen, the cells lose contact and are shed. The distal surfaces of the cells in the upper layer are lined by a surface coat which consists of finely branched filaments. The esophageal epithelium of the adult mouse is similar to the epidermis and undergoes complete keratinization. The sequential development of differentiation products, namely the cytoplasmic filaments, membrane-coating granules (MCG) and keratohyalin granules is seen as the cells migrate toward the surface. After their formation, MCG migrate toward the cell surface where they become confluent with the plasma membrane and are secreted into the intercellular space. Keratohyalin granules are also elaborated in large numbers and become dispersed as the cells become cornified. As the horny cells are formed the cell constituents such as the rough-surfaced endoplasmic reticulum, Golgi complex, ribosomes, mitochondria and the nucleus disintegrate. The fully keratinized cell has a thickened envelope and is filled with filaments embedded in an amorphous matrix.     

Scanning electron microscopy of the bursa of fabricius from normal and testosterone-treated embryos

Scanning electron microscopy (SEM) has revealed the presence of projecting follicles (PF) and button-like follicles (BLF) in the bursa of Fabricius. This study was designed to examine the embryonic bursa with SEM to ascertain which type of follicle appears first and to compare the SEM of the bursa from normal embryos with those having received testosterone propionate (TP) on the 11th day of incubation. The bursa of the latter embryos exhibits an arrested lymphoid development. PF appeared in normal embryos by 16 days and were well developed by 18 days of embryonic development. Inter-follicular epithelium was apparent by 21 days of embryonic development in normal embryos. On the other hand, bursal follicles and interfollicular epithelium failed to form in TP birds. The TP-birds exhibited a characteristic pebble-like epithelium which may attest to the regressive influence of TP on bursal epithelium or to an arrested stage of epithelial development. The PF may lead to the development of BLF or the BLF may be derived independently of PF.     

Induction of colitis in mice deficient of Peyer's patches and mesenteric lymph nodes is associated with increased disease severity and formation of colonic lymphoid patches

Inflammatory bowel disease is associated with immune activation in Peyer's patches and mucosal lymph nodes. The role of these organs in dextran sodium sulfate (DSS)-induced colitis was investigated. We used mice lacking Peyer's patches and/or lymph nodes because of lymphotoxin-alpha gene deficiency or treatment in utero with lymphotoxin-beta-receptor IgG and tumor necrosis factor-receptor-I (55)-IgG fusion proteins. Mice lacking Peyer's patches and lymph nodes because of lymphotoxin-alpha deficiency or in utero fusion protein treatment developed more severe colitis than control mice as indicated by more severe intestinal shrinking, longer colonic ulcers, and higher histological disease scores. Oral DSS triggered the formation of colonic submucosal lymphoid patches in these mice and caused an increase in the number of submucosal lymphoid patches in mice treated in utero with the fusion proteins. Mice lacking Peyer's patches only showed more submucosal lymphoid patches whereas intestinal length and histological disease score were similar to control mice. In conclusion, more severe DSS-induced colitis correlates with the loss of the mesenteric lymph nodes. However, neither the absence of Peyer's patches nor the presence of colonic lymphoid patches were correlated with increased disease severity.     

An electron microscopic study of apoptosis in the granulosa layer of ovarian follicles in rats treated with continuous illumination

Polycystic ovarian syndrome was induced in adult rats by treatment with continuous illumination to study follicular atresia. Granulosa cells of regressing antral follicles showed characteristic features of apoptosis ultrastructurally: condensed nuclei, apoptotic bodies, and phagocytosis of the apoptotic cells and their fragments by neighboring cells. In this study, moreover, it was observed that an intact granulosa cell was able to ingest another granulosa cell of normal appearance, presumably indicating an early stage of follicular atresia. The phagocytosing granulosa cell surrounded another granulosa cell to be phagocytosed by elongated cell processes. Gap junctions developed between the phagocytic cell and the phagocytosed cell. The phagocytic cell possessed abundant free ribosomes, well-developed rough endoplasmic reticulum and mitochondria, but few lysosomes. The ingested cell was similar in appearance to the phagocytic cell. In addition, granulosa cells were also observed ingesting karyopyknotic cells and degenerative organelles, both displayed in large vacuoles filled with fragments of nuclei and organelles. These findings suggest a process of apoptosis in the granulosa cells during follicular atresia. This study was presented at the 20th Annual Meeting of the Clinical Electron Microscopy Society of Japan, Fukuoka, September 1–3, 1988.     

Peyer's patches: organized lymphoid structures for the induction of mucosal immune responses in the intestine.

Peyer's patches (PP) comprise transmucosal clusters of lymphoid follicles overlaid with a specialized lympho-epithelium and consequently play a central role in the induction of mucosal immune responses in the gut. Despite considerable achievements in the last 3 decades, in our understanding of how PP are involved in the induction of immune responses, much remains to be learned about these major organized lymphoid organs. The history and current status of PP termed 'the major inductive site of immune responses' is reviewed. The present understanding of PP biology and function, taking into account their preferential and unique retention of immune competent cells at specific sites, is discussed.     

Purine metabolism and B-lymphocyte development in the chicken bursa of fabricius.

The activity of three enzymes involved in the salvage pathway of purine nucleosides--purine nucleoside phosphorylase (PNP), xanthine dehydrogenase (XDH), and hypoxanthine-guanine phosphoribosyl transferase (HGPRT)--was investigated in cellular fractions of the chicken bursa of Fabricius differentially enriched in epithelial cells or lymphocytes. Markedly increasing levels of PNP and XDH were observed along with the enrichment in epithelial cells together with a slight, though significant, decrease in HGPRT activity. By contrast, a dramatic fall in PNP and XDH activities was detected along with the enrichment in lymphocytes together with a slight, though significant, increase in HGPRT activity. This sharply different distribution of the three enzymes, all sharing hypoxanthine as a substrate, clearly indicates that lymphocytes preferentially channel hypoxanthine into the salvage and interconversion pathways, phosphorylating it to IMP, while epithelial cells rapidly catabolize such a purine base to uric acid. Moreover, epithelial cells, unlike lymphocytes, are able to retain high intracellular levels of both hypoxanthine and inosine. These results support the possibility that epithelial cells contribute to the normal development of bursal lymphocytes by supplying such actively proliferating cells with purine rings and at the same time by preventing them from accumulating potentially toxic high levels of purine nucleotides being able to rapidly eliminate excess hypoxanthine as uric acid from the bursa environment into the bloodstream.     

Myofibroblasts in fibromatoses. An electron microscopic study

Fifteen cases of fibromatoses were analyzed by electron microscopy, the objective being to compare the incidence and frequency of myofibroblasts in each category. Myofibroblasts were identified in all 15 cases and a considerably large number of these cells appeared in palmar fibromatosis, plantar fibromatosis, and nodular fasciitis. In keloid and cicatricial fibromatosis, however, only a small number of these cells were evident. In seven cases of extra-abdominal desmoid fibromatosis, the frequency of myofibroblasts in the component cells ranged from 10% to 64%, with a mean of 30%. The frequency was high in hypercellular lesions and low in hypocellular lesions, assuming that it would be roughly in parallel to the cellularity of the lesion in extra-abdominal desmoid fibromatosis and in other fibromatoses as well. There appeared to be no particular correlation between the number of myofibroblasts and recurrence of the lesion.