The development of the human tonsilla palatina

Summary Tonsils of human fetuses at the 8th to the 28th gestational week (g.w.) were investigated by electron microscopy, enzyme histochemistry, and immunohistochemistry on cryostat sections. The development of the tonsilla palatina starts during the 14th g.w. when the mesenchyme underlying the mucous membrane of the tonsillar cavity becomes invaded by mononuclear wandering cells. In fetuses of about the 16th g.w. epithelial crypts grow down into the connective tissue and are infiltrated by T-lymphocytes. At the same time, precursors of interdigitating cells (IDC) can be identified among the epithelial cells. Frequently, lymphocytes and IDC-like cells are in close contact. From these findings it is concluded that the infiltrated crypt epithelium in the human tonsilla palatina represents a T-cell region. Primary follicles develop in earlier fetal stages than in all other secondary lymphoid organs. They contain precursors of dendritic reticulum cells and lymphoid cells that belong to the B-cell line. These primary follicles may be considered as the first assemblage of B-cell regions in human fetal lymphoid tissue. The present findings indicate that the formation of different stationary elements during the development of B-cell regions and T-cell regions is an important factor for the homing and antigen-dependent maturation of different subpopulations of immunocompetent lymphoid cells.This investigation was supported by grants from the Deutsche Forschungsgemeinschaft, particularly the Sonderforschungsbereich 111The authors appreciate the contribution of human fetal material from Dr. J. von Hollweg and Dr. J. Körner from the Hospital Heidberg c.o. Hamburg and the excellent technical assistance of Mrs. O.-M. Bracker, Mrs. H. Hansen, Mrs. I. Knauer, Mrs. R. Köpke, Mrs. I. König, Mrs. F. Müller, Mrs. H. Siebke and Mrs. H. Waluk     

Ontogeny and organization of the stationary non-lymphoid cells in the human thymus

Summary Ontogenetic differentiation of the human thymus was investigated in 50 embryos by means of light and electron microscopic methods in an attempt to clarify the morphogenesis of the complicated microecology of thymic tissue. At the 8th gestational week (g.w.), the primordium of the thymus contains almost exclusively undifferentiated epithelial cells. At the 10th g.w., the epithelial cells in the central part are spindle-shaped. During the subsequent weeks the cortical region of the thymus becomes separated into lobes by mesenchymal septa containing hemopoietic precursor cells and large electronlucent cells with irregularly shaped nuclei. The latter cells are also found in the deeper presumptive medullary regions of the thymus; they differentiate into interdigitating reticulum cells (IDC). The permeation of the medulla of the thymus by non-epithelial IDC occurs concurrently with the formation of cortical and medullary epithelial cells. Between the 12th and 14th g.w. the cortical and medullary differentiation is completed. At this time-stage cortical small lymphocytes differ in morphological shape from medullary lymphocytes, the latter acquiring the appearance of immunocompetent T cells and establishing intimate contact with the IDC.These findings indicate that the thymic cortex and medulla contain different epithelial cells. In addition, the thymic medulla displays cells characterized by the morphology of typical interdigitating reticulum cells of peripheral lymphoid tissue. The structural pattern of the thymus is correlated to morphologically differing lymphoid cell populations in the cortical and medullary regions.This investigation was supported by grants from the Deutsche Forschungsgemeinschaft and by the Sonderforschungsbereich 111The authors dedicate this paper to Professor Helmut Leonhardt on the occasion of his 60th birthday. The authors also appreciate the excellent technical assistance of Mrs. I. Knauer, Mrs. H. Waluk and Mrs. H. Siebke     

The development of the human spleen

Summary Splenic tissue of human fetuses from the 14^th to the 24^th week of gestation (menstrual age) were investigated by light- and electron microscopy to describe the development of the red and white pulp in close relationship to the differentiation of the vascular tree. Special interest is focussed on the differentiation of the T-cell- and the B-cell regions and their specific stationary cells.The preliminary stage, here called the primary vascular reticulum, lasts up to the 14^th gestational week (gw). Numerous erythrocytes, normoblasts and macrophages are seen among a network of mesenchymal cells and argyrophilic fibers. Hematopoiesis, especially erythropoiesis, can be recognized.The characteristic organ structure becomes established during the subsequent transformation stage of the fetal spleen, beginning with the 15^th gw. Splenic lobules begin to form during the 15^th to 17^th gw. They consist of a central artery, surrounded by a sheath of lightly stained stationary cells which resemble myofibroblasts. At the periphery of these lobules the red pulp forms. Initially mobile cells are distributed throughout the reticulum. Soon they begin to accumulate in the venous sinuses, which develop from lacunae among the reticular network and come into contact with the venous system. The endothelial wall of these sinuses remains discontinuous, confirming the theory of the open vascularization of the spleen. The development of the larger veins is correlated with the differentiation of the splenic trabeculae.The development of the white pulp is correlated with the stage of lymphoid colonization within the spleen, beginning around the 18^th gw. An accumulation of lymphocytes around the central arteries can be recognized during the 19^th and 20^th gw. These lymphoid cells show morphological and immunohistochemical characteristics of T-precursor cells. Within the now assembling periarterial lymphoid sheath (PALS) a few precursors of interdigitating cells (IDC) are recognizable, giving evidence for the differentiation of the T-cell region.Around the 23^rd gw the assemblage of primary follicles is discernible at the periphery of the PALS. Precursors of the follicular dendritic reticulum cell (FDRC), the specific stationary cell of the B-cell region, have been recognized. This observation leads to the conclusion that the small primary follicles represent the beginning formation of the B-cell region.The significance of the vascular system for the differentiation of the specific splenic organization is discussed.This investigation was supported by grants from the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 111)The authors appreciate the contribution of human fetal material from Dr. von Hollweg and Dr. Körner from the Hospital Heidberg, Hamburg, and the excellent technical assistance of Mrs. H. Hansen, Mrs. I. Knauer, Mrs. M.v. Kolszynski, Mrs. J. Quitzau, Mrs. H. Siebke and Mrs. H. Waluk     

An electron microscope autoradiographic study of DOC conversion to corticosterone in the rat adrenal cortex

Summary Seven thymuses from children between 1 and 12 years were examined by electron microscopy. Biopsies had been taken during surgical correction of congenital heart defects.In all cases we found interdigitating reticulum cells (IRC) in the medulla and inner cortex. These cells resembled the IRC which have been described previously in the thymus-dependent regions of the spleen and lymph node. They were characterized by an irregularly shaped nucleus, narrow cisterns of rough endoplasmic reticulum, and widespread interdigitation and invagination of the cell membrane. The surfaces of the IRC were in close contact with those of small lymphocytes, sometimes polysomal lymphatic cells, epithelial cells, and occasionally with those of lymphatic cells containing ergastoplasm.The IRC is apparently a specific cell of thymus-dependent regions. It may be that the IRC in the thymus, lymph node, and spleen contribute to the microenvironment needed for the differentiation of T-cells.Supported by the Deutsche Forschungsgemeinschaft, SFB 111/CII and III.—We wish to thank Miss M. Neubert and Mrs. R. Köpke for their technical assistance and Mrs. M. Soehring for her help with the translation.     

On the interdigitating cells in the thymus-dependent area of the rat spleen: A relation between the mononuclear phagocyte system and T-lymphocytes

Summary Light- and electron microscopic studies reveal that the peri-arteriolar lymphocytic sheath of the rat spleen can be divided into two areas. The central area contains small lymphocytes, interdigitating cells (IDC, light staining cells with extensive cytoplasmic interdigitations) and some scattered reticulum cells. The peripheral area contains a mixed population of lymphocytes and circumferentially oriented reticulum cells. It is shown that only the central area of the peri-arteriolar lymphocytic sheath is thymus-dependent. In neonatally thymectomized rats, before interdigitating cells appear, monocytes and promonocytes reside in this area. It is suggested that the IDC are part of the mononuclear phagocyte system (Langevoort et al., 1970). They probably form the micro-environment necessary for the differentiation and proliferation of T-cells. The analogies between IDC, epithelioid cells and the macrophages in the migration inhibition test are discussed. The hypothesis is put forward that these cells are similar in ultrastructural and functional aspects because all three are macrophages under the influence of humoral factors from T-cells, such as migration inhibition factor.The author wishes to thank Prof. Dr. H. L. Langevoort for advice and stimulating discussion Dr. E. C. M. Hoefsmit for hospitality in the Department for Electron Microscopy of the Faculty of Medicine of the Free University; Mrs. D. Reichelt-Horaková for technical and Miss E. M. Ligtvoet for secretarial assistance.     

A comprehensive immunotopographic map of human thymus

We have achieved a comprehensive immunotopographic mapping of human thymus by using a large battery of monoclonal antibodies and the methodological refinement of comparative serial tissue section immunohistochemistry, allowing analysis of multiple phenotypes in the same tissue site. Previous immunohistochemical studies of thymus have concentrated on the majority T-cell and epithelial cell populations. Besides demonstrating the complexity of T-cell antigenic expression (e.g., simultaneous cortical expression of Leu 2, Leu 3, CALLA, Tdt, and Leu 6), we delineate surprisingly complex B-cell zones (e.g., septal B-follicles with DRC+C3d+ dendritic cells and zonal maturation of B-cells). Whereas septal B-follicles were found in 25% of cases, medullary B-cells were universally present as a substantial minority component. This expanded immunotopographic knowledge of the complex T-, B-, epithelial, and reticulum cell neighborhoods suggests that the thymus is an organ capable of a broad repertoire of immunological responses, not limited to T-cell development.     

The villous stroma of the human placenta

Summary In human placental villi the connective tissue is constructed by mesenchymal cells, small and large reticulum cells and fibroblasts. During early pregnancy mesenchymal cells dominate; starting with the third month of gestation the reticulum cells are in the majority within the terminal villi, the fibroblasts within the stem villi. Ultrastructurally intermediary types of cells can be differentiated. Together with reticular and collagenous fibres the reticulum cells form the basic architecture of the villous stroma during the first 2/3 of gestation: the reticular type of stroma. This consists of a network of cells and fibres with fetal vessels fitted in between. The remaining interspaces form a fluid system of compartments in which Hofbauer cells are suspended. They are called stromal channels. During the last trimester these channels and the Hofbauer cells as well are progressively replaced either by voluminous masses of fibres (fibrous type of stroma, mainly in the stem villi) or by sinusoidal enlargements of fetal capillaries (sinusoidal type of stroma, mainly in the terminal villi).Supported by grants from the Deutsche ForschungsgemeinschaftThe authors are indebted to Mrs. E. Böhm and Mrs. E. Schäfer for skilful technical assistance     

Human dendritic reticulum cells of lymphoid follicles: their antigenic profile and their identification as multinucleated giant cells

The B-dependent areas of human lymphoid tissue contain non-lymphoid, non-phagocytic cells known as dendritic reticulum cells (DRC). These cells can be detected only very occasionally in routinely stained histologic sections. Recently we were able to overcome this limitation by preparing a monoclonal antibody, termed R 4/23, that reacts selectively with DRC. Thus by using an optimized immunoperoxidase method applied to frozen sections, it is possible to detect DRC in situ. To determine the antigenic profile of DRC, serial frozen sections of human tonsils were immunostained with R 4/23 and a large panel of other monoclonal antibodies or conventional antisera. In addition, touch imprints of tonsils and cytocentrifuge slides of cell suspensions with increased concentrations of DRC were immunostained with these reagents. DRC proved to be positive for mu, gamma, alpha, kappa and lambda chains, complement component C3b, C3b receptors, C3d receptors, HLA-A,B,C antigens, human Ia-like antigens, common ALL antigen (cALLa), and antigens that are characteristic of the monocyte/macrophage lineages. DRC did not express delta chains, T cell antigens, or antigens that are expressed on interdigitating reticulum cells (IDC) and Langerhans cells. DRC in touch imprints and suspensions prepared from hyperplastic tonsils were found to be giant cells often with 10 or more nuclei. In certain cases of follicular hyperplasia and of centroblastic-centrocytic lymphoma, DRC with several nuclei were also detectable in situ. These results show that (1) the phenotype of DRC differs from that of all other cell types in lymphoid tissue, (2) this phenotype most nearly resembles that of cells of the monocyte/macrophage series, thus suggesting that DRC are related to these cell lineages, and (3) DRC are multinucleated giant cells.     

Regulation of human B-cell colony growth

PHA-induced B-cell enriched populations from venous blood of healthy adults developed into B-cell colonies. Analyses of individual colonies revealed that 80-85% of the cells in each colony were surface membrane immunoglobulin positive. Most colonies, 84%, contained surface IgM-bearing cells. Only a few, 16%, were found with surface IgG-bearing cells. Surface IgM- and surface IgG-bearing cells were not observed in the same colony. Thirty-nine percent of the colonies contained cells bearing surface IgD in addition to either surface IgM- or surface IgG-bearing cells. There was no evidence of cytoplasmic immunoglobulin in the colony cells. The development of B-cell colonies was T-cell dependent; it appears that at least two different T-cell subpopulations, one with low density (D = 1.05) and the other with high density (D = 1.08) are responsible for this helper effect. Monocytes were found to inhibit B-cell colony formation; the inhibition was mainly by endogenous prostaglandin E2 (PGE2) synthetized and released by monocytes. The addition of physiological concentrations of synthetic PGE2 to monocyte-depleted B-cell enriched populations inhibited B-cell colony growth, this paralleled the effect of endogenous PGE2 released by monocytes. Indomethacin (10-5 M) obviated the inhibitory effect of monocytes.     

Phenylalanine ammonia-lyase and chalcone synthase in glands ofPrimula kewensis (W. Wats): immunofluorescence and immunogold localization

Phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) were localized by indirect immunofluorescence and immunogold labeling in glands ofPrimula kewensis. Both enzymes were exclusively present in the head cells of the glands. Phenylalanine ammonialyase was located in the regions of the dense tubular endoplasmic reticulum and occasionally found in more or less spherical organelles that have not yet been identified. Furthermore, an appreciable proportion of the enzyme protein was associated with the plasmalemma and the cell wall of the head cell. In contrast, the occurrence of CHS was restricted to the spherical, unidentified cell compartments. Our findings indicate that the gland cells have the potential for flavonoid biosynthesis. When a mutant ofP. kewensis forming structurally intact glands but incapable of farina excretion was studied, neither PAL nor CHS were found in the head cells.Abbreviations CHS chalcone synthase - IgG immunoglobulin G - PAL phenylalanine ammonia-lyase Financial support from the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie is gratefully acknowledged. We are grateful to Mrs. Karin Schlattmann and Mrs. Susanne Otter for preparing the ultrathin sections and to Mrs. Marianne Opalka for taking the photographs.     

Interdigitating reticulum cells in lymph nodes of Sézary syndrome. Freeze-fracture and ultrathin-section morphology

Lymph nodes with extensive leukemic infiltration from three patients with the Sézary syndrome were examined in ultrathin sections and in freeze-fracture replicas. Sézary cells (SC) and interdigitating reticulum cells (IDC) were the predominant cell types in the lymph nodes. Both were closely connected with each other by apparently interdigitating cytoplasmic processes. The projections between these cells were, in the main, processes from the IDC. In freeze-fracture replicas these cellular processes did not appear as interdigitations but were more bubble-like, and for this reason these cells are imprecisely described by the term "interdigitating." The SC were seen to possess only short cytoplasmic processes. The frequent polar grouping of cell organelles in SC in the region of the contact zone with IDC and the high organelle content of IDC ('activated IDC') could be the morphologic expression of intense interaction between IDC and SC. IDC displayed three features in freeze-fracture which are not specific to the Sézary syndrome, but should be applicable to IDC in general: (1) they exhibited an approximately equal density of intramembrane particles in both the E-face and the P-face, (2) some of the intramembrane particles in the P-face were assembled in clusters and (3) the surface showed bubble-like formations of the cytoplasmic processes. On the basis of these properties it was possible to distinguish IDC from macrophages and lymphocytes in freeze-fracture replicas.     

Ultrastructure of the age-involuted adult human thymus

Summary Age involuted thymus tissue from a middle aged (33 years) and an old (63 years) man have been examined by electron microscopy and compared with thymus tissue from children. Biopsies had been taken during surgical correction of congenital heart defects.The fine structural architecture of cortex, medulla and connective tissue in the remaining lymphatic islands in the adult thymus investigated was not different to the thymus of children. We were surprised to find vigorous lymphocytopoiesis in the cortical regions and to recognize extended areas of medulla with a cellular composition which obviously provides the same microenvironment for T-cell maturation as the medulla of the non involuted thymus. Our findings are discussed in relation to the increasing arguments that the human thymus serves an immunological function throughout life.This investigation was supported by grants from the Deutsche ForschungsgemeinschaftI express my thanks to Professor Dr. med. Alexander Bernhard (Kiel) for kindly providing the human thymus tissue. The author also appreciates the excellent technical assistance of Mrs. Knauer, Mrs. Parczany, Mrs. Siebke and Mrs. Waluk     

Non-lymphoid cells of bronchus-associated lymphoid tissue of the rat in situ and in suspension

Immunohistochemical, enzyme-histochemical and electron-microscopical methods were used to study non-lymphoid cells of control and stimulated rat bronchus associated lymphoid tissue (BALT) in situ and in suspensions. Particular attention was paid to the so-called antigen-handling cells, i.e., the interdigitating cells (IDC), which are situated in the T-cell areas, the follicular dendritic cells (FDC), which appear to be restricted to germinal centers, and macrophages, present both in T-cell and B-cell areas. The interdigitating cells were distinguished by being Ia-positive and by the presence of acid phosphatase and non-specific esterase activity in an area near the nucleus. Follicular dendritic cells could be observed in situ by using a monoclonal antibody and by the in vitro trapping of HRP-anti-HRP complexes. Several types of macrophages were found. At the electron-microscopical level no well-developed IDC and FDC could be detected in control BALT. However, in BALT of lipopolysaccharide-stimulated and mycoplasma-infected rats, well-developed IDC and FDC were found. It can be concluded that IDC's and FDC's can be found in BALT.     

Peroxidase-positive mononuclear leukocytes as possible precursors of human dendritic reticulum cells

In this report, we provide evidence that suggests the dendritic reticulum cells (DRC) occurring in germinal centers of lymphatic follicles originate from a distinct endogenous peroxidase-positive mononuclear blood cell subset. The new monoclonal antibody Ki-M4 showed a highly restricted reactivity, tested by immune histochemistry, being confined to DRC, lining cells of lymph node sinuses, and to 0.001% of nonadherent mononuclear blood cells separated at a density of 1.077 g/ml; the latter exhibited endogenous peroxidase activity in cytoplasmic granules. Such granules being specific for myelomonocytic cells implies that DRC may derive from a committed nonadherent subpopulation of this cell line, which in turn originates from bone marrow. The Ki-M4-reactive antigen was found to be destroyed by the majority of fixatives and to resist 4% paraformaldehyde for 10 min and cold acetone for 30 sec. In cell suspensions from human tonsils, Ki-M4 showed strong reactivity with the outer surface of DRC plasma membrane. This observation demonstrates the possibility of using Ki-M4 to separate DRC from cell suspensions in functional tests.     

Induction of interdigitating reticulum cell-like differentiation in human monocytic leukemia cells by conditioned medium from IL-2-stimulated helper T-cells

Monocytic leukemia (MoL) cells were obtained from the peripheral blood of a patient in whom the leukemic cells infiltrating various lymphoreticular organs exhibited features intermediate between interdigitating reticulum cells (IDC) and ordinary phagocytic macrophages, whereas the leukemic cells in the peripheral blood were essentially monocytic and lacked such features. Peripheral blood CD4+ T-cells were established as an interleukin-2-dependent T-cell line. When the MoL cells were exposed for a few days to conditioned medium from the T-cell line, they extended several dendritic cytoplasmic projections and became intensely positive for HLA-DR antigen, cytoplasmic S-100β protein, and CD1 antigen. Functionally, the conditioned medium significantly down-regulated Fc-mediated and Fc-independent phagocytic activities, and the levels of lysosomal enzymes such as lysozyme and nonspecific esterase in the MoL cells. Moreover, the conditioned medium significantly up-regulated the accessory cell function of the MoL cells as measured by the primary allogenic mixed leukocyte reaction (MLR). Furthermore, the conditioned medium significantly down-regulated the expression of CD14 antigen. Biochemical analysis indicated that the factor responsible for these changes is a protein which is distinct from known human cytokines and whose molecular weight is approximately 31 kDa. These findings suggest that IDC are closely related the monocytic lineage and that helper T-cells play an important role in constructing the microenvironment of T-lymphoid tissues which is necessary for the differentiation and maturation of IDC.     

Morphological characterization of stationary reticulum cells of the stromal in the mesenteric lymph node of the guinea pig

The large mesenteric lymph node taken from guinea pigs in a period of time ranging from the 10th day prepartum till the 26th day postpartum has been examined in order to study: the morphological features of the stromal stationary reticulum cells with particular regard to recognize their stages of development; the possible ontogenetic relationship between these cells during the maturation of the lymphoid tissue. Our data support the hypothesis that from local mesenchymal cells originates a pool of poorly differentiated reticulum cells that can give rise to stromal stationary reticulum cells (myofibroblast-like cells, fibroblast-like cells, pericyte-like cells and dendritic cells). These elements have a characteristic distribution pattern likely related to different local functional requirements.     

Human mesenchymal stem cells inhibit the differentiation and effector functions of monocytes

Although monocytes represent an essential part of the host defence system, their accumulation and prolonged stimulation could be detrimental and may aggravate chronic inflammatory diseases. The present study has explored the less-understood immunomodulatory effects of mesenchymal stem cells on monocyte functions. Isolated purified human monocytes were co-cultured with human umbilical cord-derived mesenchymal stem cells under appropriate culture conditions to assess monocytes’ vital functions. Based on the surface marker analysis, mesenchymal stem cells halted monocyte differentiation into dendritic cells and macrophages and reduced their phagocytosis functions, which rendered an inability to stimulate T-cell proliferation. The present study confers that mesenchymal stem cells exerted potent immunosuppressive activity on monocyte functions such as differentiation, phagocytosis and Ag presentation; hence, they promise a potential therapeutic role in down-regulating the unwanted monocyte-mediated immune responses in the context of chronic inflammatory diseases.     

Monoclonal antibodies identifying a novel T-Cell antigen and Ia antigens of human lymphocytes

We describe here two new monoclonal antibodies that react with surface antigens of human lymphocytes. Antibody 7.2 identified a determinant on the framework region of the human Ia antigen. It was cytotoxic for all cultured B-cell lines, normal B cells, and monocytes. The antibody was not cytotoxic for normal T cells or for established T leukemic cell lines. In immune precipitation assays, the 7.2 antibody reacted with a bimolecular complex of two chains that resolved in polyacrylamide gels as polypeptides with molecular weights of 29000 and 34000 daltons. These precipitation results were analogous to those achieved with a rabbit antiserum prepared against human Ia antigens. Antibody 9.3 identified a determinant on the framework region of a T-cell antigen. It was cytotoxic for 50–80% of peripheral T cells and for 20–50% of thymocytes. It was not cytotoxic for cultured B-cell lines, normal B cells, or monocytes. In immune precipitation assays, the 9.3 antibody reacted with a single polypeptide with a molecular weight of 44000 daltons. Due to the expression of this antigen on a limited subpopulation of human T cells, we have designated the antigen HuLyt-1.     

Induction of interdigitating reticulum cell-like differentiation in human monocytic leukemia cells by conditioned medium from IL-2-stimulated helper T-cells.

Monocytic leukemia (MoL) cells were obtained from the peripheral blood of a patient in whom the leukemic cells infiltrating various lymphoreticular organs exhibited features intermediate between interdigitating reticulum cells (IDC) and ordinary phagocytic macrophages, whereas the leukemic cells in the peripheral blood were essentially monocytic and lacked such features. Peripheral blood CD4+ T-cells were established as an interleukin-2-dependent T-cell line. When the MoL cells were exposed for a few days to conditioned medium from the T-cell line, they extended several dendritic cytoplasmic projections and became intensely positive for HLA-DR antigen, cytoplasmic S-100 beta protein, and CD1 antigen. Functionally, the conditioned medium significantly down-regulated Fc-mediated and Fc-independent phagocytic activities, and the levels of lysosomal enzymes such as lysozyme and nonspecific esterase in the MoL cells. Moreover, the conditioned medium significantly up-regulated the accessory cell function of the MoL cells as measured by the primary allogenic mixed leukocyte reaction (MLR). Furthermore, the conditioned medium significantly down-regulated the expression of CD14 antigen. Biochemical analysis indicated that the factor responsible for these changes is a protein which is distinct from known human cytokines and whose molecular weight is approximately 31 kDa. These findings suggest that IDC are closely related the monocytic lineage and that helper T-cells play an important role in constructing the microenvironment of T-lymphoid tissues which is necessary for the differentiation and maturation of IDC.     

Distribution of dendritic reticulum cells in follicular lymphoma and reactive hyperplasia. Light microscopic identification and general morphology

Reactive and neoplastic follicles in lymph nodes showing changes of (1) follicular hyperplasia and (2) follicular lymphoma were examined for the presence of dendritic reticulum cells (DRC). These cells could be identified under the light microscope after comparing electron microscopical sections with subsequent 1 micro sections of reactive germinal centres. Quantitative light microscopical evaluation showed that DRC, both mononuclear and binuclear forms, were less numerous in neoplastic follicular structures than in reactive follicles. Before determining the frequency of binucleated DRC in follicular tissue their morphology was studied first in cell suspensions. DRC isolated by enzymatic treatment of tonsils and reactive lymph nodes were morphologically identical and contained one, or at most two, nuclei arranged in a typical doublet formation. Stereological calculations - made on three dimensional models of nuclear complexes prepared from serial tissue sections - indicated that 51 to 68% of DRC in reactive germinal centres were binucleated, whereas in neoplastic follicles this figure is 18 to 23%. The multinucleated giant cell forms of DRC described by others result from complex formation with other DRC or lymphoid cells. The smaller number of DRC and the lower frequency of binucleated DRC in follicular lymphomas suggest that differentiation of DRC from stromal cells is less complete in these neoplasms. The ability to identify DRC reliably by light microscopy offers a new means to define the difference in frequency of DRC. This may be of practical value in distinguishing reactive germinal centres from neoplastic follicles.