Dendritic reticulum cells in reactive lymph nodes and tonsils: an immunohistological study

There has recently been much interest in the patterns of follicular dendritic reticulum cells (DRC) in pathological lymph nodes, particularly in relation to the phenomenon of DRC break-up (thought to be pathognomonic of AIDS-related lymphadenopathies) and to progressive transformation of germinal centres (as a possible precursor of lymphocyte predominant Hodgkin's disease). In the present study we have immunostained twenty-nine reactive lymph nodes and five tonsils with monoclonal antibody R4/23 (DAKO-DRC) in order to evaluate the frequency of such changes in lymphoid tissue unaffected by AIDS or Hodgkin's disease. Most of the specimens contained typical secondary follicles with clearly defined germinal centres and mantle zones. There were two variants in lymph nodes showing follicular hyperplasia characterized by (i) progressive transformation of germinal centres and (ii) inclusions of nests of small lymphocytes within germinal centres. In each of these types of follicles the compact evenly-distributed meshwork of DRCs, as previously described, was seen. However there were considerable variations in DRC meshwork in each category (the pattern could not be predicted from the morphology) with examples in all three of the DRC break-up previously considered specific for the AIDS related lymphadenopathy. Since none of the lymph nodes and tonsils studied had any known relationship to either Hodgkin's disease or AIDS it is argued that none of the changes in the DRC meshwork observed are specific for these conditions.     

Innate lymphoid cells in secondary lymphoid organs

The family of innate lymphoid cells (ILCs) has attracted attention in recent years as its members are important regulators of immunity, while they can also cause pathology. In both mouse and man, ILCs were initially discovered in developing lymph nodes as lymphoid tissue inducer (LTi) cells. These cells form the prototypic members of the ILC family and play a central role in the formation of secondary lymphoid organs (SLOs). In the absence of LTi cells, lymph nodes (LN) and Peyer's Patches (PP) fail to form in mice, although the splenic white pulp can develop normally. Besides LTi cells, the ILC family encompasses helper-like ILCs with functional distinctions as seen by T-helper cells, as well as cytotoxic natural killer (NK) cells. ILCs are still present in adult SLOs where they have been shown to play a role in lymphoid tissue regeneration. Furthermore, ILCs were implicated to interact with adaptive lymphocytes and influence the adaptive immune response. Here, we review the recent literature on the role of ILCs in secondary lymphoid tissue from the formation of SLOs to mature SLOs in adults, during homeostasis and pathology.     

Conjunctiva-associated lymphoid tissue in avian mucosal immunity

Conjunctiva-associated lymphoid tissue’s (CALT) role in generating avian mucosal adaptive immunity was measured by analyzing cellular composition, expression of the polymeric immunoglobulin receptor (pIgR), and production of cytokines and antibodies in chickens ocular exposed to a replication-deficient adenovirus of serotype 5 (Ad5). These studies demonstrate that CALT contains B cells, γδ T cells, T helper, and cytotoxic T cells, and a T lymphocyte composition, which more resembles Harderian glands than spleen. CALT-derived lymphocytes contain antigen-specific, IgA-secreting plasma cells and cytokine-producing lymphocytes after ocular Ad5 vaccination. The expression of the pIgR in the CALT’s lymphoepithelium emphasizes the importance of mucosal immune protection by paraocular lymphoid tissues. The CALT immune response after ocular Ad5 boosting was influenced by prior high dose in ovo Ad5 priming. Thus, both mucosal and systemic immunization influenced Ad5-induced IFN-γ responses in CALT.     

Distribution of lymphoid tissue in the caecal mucosa of chickens

In order to clarify the fundamental structure of the host defence mechanism in chicken caeca, a detailed analysis of the distribution of lymphoid nodules (LNs) was carried out on longitudinal sections of both the mesenteric (side of the ileocaecal ligament) and the antimesenteric mucosa. An overwhelming majority of solitary or aggregated LNs were located in the mesenteric mucosa, although a few were also found in the antimesenteric mucosa. Of the total LNs, 45.7% were detected at the proximal 7.8% section in the caecal tonsil. LNs (21.4%) were also concentrated in the distal 22.0% section corresponding to the apex. A moderate concentration of LNs (13.1%) was found at the transitional 20.0% region between the base and body. Approximately 80.2% of total LNs were found at the above 3 regions in the mesenteric mucosa. In many cases, the frequency of LNs in the caecal tonsils was opposite to that at the apices. Aggregated LNs were mainly found in the caecal tonsils, transitional region and apex. Almost all aggregated LNs consisted of fundamental nodular units possessing M cells in their follicle associated epithelia. The aggregated LNs in the above 3 regions therefore could provide immunological surveillance against caecal luminal contents. In particular, the cooperative function between LNs of the caecal tonsil and apex might be highly important in maintaining the caecal microenvironment.     

Warthin-Finkeldey-like cells in benign and malignant lymphoid proliferations

Multinucleate giant cells resembling Warthin-Finkeldey cells have been described in various lymphoid disorders. These Warthin-Finkeldey-like cells (WFLC) with as many as 50 nuclei are of three main types: reticular, lymphocyte and intermediary. In reactive lymphoid proliferations (34 cases) WFLC were mainly observed inside germinal centres and to a lesser extent in the interfollicular zones. In neoplastic lymphoid proliferations (33 cases) WFLC were most commonly found in the lymphocytic predominance type of Hodgkin's disease (16/25 cases). All non-Hodgkin's lymphomas (13 cases) in which WFLC were detected proved to be of low grade malignancy (lymphocytic: one case, lymphoplasmacytic-plasmacytoid: six cases; and centroblastic-centrocytic, six cases). They were also found in two cases of angioimmunoblastic lymphadenopathy. Immunoperoxidase and electron microscopic studies could not elucidate the exact histogenesis of these cells, but it is assumed that they are associated with B cell proliferations.     

Flow cytometric analysis of immunoglobulin heavy chain expression in B-cell lymphoma and reactive lymphoid hyperplasia

The diagnosis of B-cell lymphoma (BCL) is often dependent on the detection of clonal immunoglobulin (Ig) light chain expression. In some BCLs, the determination of clonality based on Ig light chain restriction may be difficult. The aim of our study was to assess the utility of flow cytometric analysis of surface Ig heavy chain (HC) expression in lymphoid tissues in distinguishing lymphoid hyperplasias from BCLs, and also differentiating various BCL subtypes. HC expression on B-cells varied among different types of hyperplasias. In follicular hyperplasia, IgM and IgD expression was high in mantle cells while germinal center cells showed poor HC expression. In other hyperplasias, B cell compartments were blurred but generally showed high IgD and IgM expression. Compared to hyperplasias, BCLs varied in IgM expression. Small lymphocytic lymphomas had lower IgM expression than mantle cell lymphomas. Of importance, IgD expression was significantly lower in BCLs than in hyperplasias, a finding that can be useful in differentiating lymphoma from reactive processes.     

乳腺粘膜相关型淋巴瘤临床病理观察

目的：探讨乳腺粘膜相关性淋巴瘤（MALT-ML）的病理特征。方法：对4例乳腺MALT-ML的手术根治及（或）活检标本做常规石蜡切片、HE染色和免疫组化ABC法标记。结果：4例乳腺MALT-ML中2例为CCL细胞型,1例为CCL细胞型向母细胞样转化,另1例炎单核样B细胞型。4例均显示B细胞单克隆性及滤泡克隆化和淋巴上皮病变。结论：乳腺MALT-ML有与其他部位MALT-ML相似的形态特征。     

大鼠严重烫伤淋巴组织细胞凋亡的原位TUNEL及电镜观察

目的：观察严重烧伤后大鼠淋巴组织内细胞凋亡状况。方法：采用大鼠３０％体表面积Ⅲ度烫伤模型，应用原位组织ＴＵＮＥＬ技术及透射电镜，分别观察烫伤后３、６、１２ｈ３个时相点大鼠胸腺、脾、肠系膜淋巴结凋亡细胞的分布、定位和形态特征。结果：烫伤后６、１２ｈ，在胸腺、脾、肠系膜淋巴结出现明显的细胞凋亡，并见其呈散在分布于胸腺的皮质，脾的白髓及肠系膜淋巴结的皮质淋巴小结之间。结论；严重烫伤可致大鼠淋巴组织的细胞     

Roles of embryonic and adult lymphoid tissue inducer cells in primary and secondary lymphoid tissues

The nomenclature "embryonic lymphoid tissue inducer (LTi) cell" reflects the fundamental role of the cell in secondary lymphoid tissue organization. In addition, it is equally important in primary lymphoid tissue development as it regulates central tolerance to self-antigens in the thymus. An adult LTi cell constitutively expresses two sets of tumor necrosis factor (TNF) family members, whereas its embryonic counterpart expresses only one. The first set is lymphotoxin (LT)alpha, LTbeta, and TNalpha, which are essential for the secondary lymphoid organogenesis during embryogenesis and for maintaining an organized secondary lymphoid structure during adulthood. The second set is OX40- and CD30-ligands, which are critical for memory T cell generation. Adult LTi cells regulate adaptive immune responses by providing LTbetaR signals to stromal cells to maintain secondary lymphoid tissue structure, and determine adaptive immune responses by providing OX40 and CD30 survival signals to activated T cells in memory T cell generation. Along with the consideration of the roles of embryonic LTi cells in primary and secondary lymphoid tissues, this review highlights the roles of adult LTi cells in secondary lymphoid tissue function.     

Cellular composition of pancreas-associated lymphoid tissue during human fetal pancreatic development

AIM: To study human fetal pancreatic tissue between 15 weeks of gestation and term, analysing the development of pancreatic lymphoid tissue and focusing on the presence and maturational status of dendritic cells (DCs). During normal human fetal pancreatic development lymphoid tissue arises in and around the pancreas. DCs are antigen-presenting cells which are capable of initiating immunity, but are also essential in inducing and maintaining T-cell tolerance. METHODS AND RESULTS: First, the presence and general composition of intra- and peripancreatic lymphoid tissue was investigated by histology and immunohistochemistry with antibodies to CD3, CD4, CD8, CD14, CD20, CD68, and CD79. Intrapancreatic lymphoid tissue (IPLT) appeared to be present only from 29 weeks of gestation onwards, and had a similar composition to peripancreatic lymphoid tissue (PPLT), which was found in all 23 specimens examined. Both forms of lymphoid tissue had an architecture similar to lymph nodes, with separate B- and T-lymphocyte areas and scattered macrophages. DCs were investigated in detail by immunohistochemistry for CD1a, CD83, CD86, CD123, Langerin, and DC-LAMP. Both Langerin, a marker for immature DCs, as well as DC-LAMP, a marker for mature DCs, were expressed by cells in both the IPLT and PPLT at all ages examined. CONCLUSION: The presence of DCs at all developmental stages, expressing various maturation-related markers, in addition to the general composition of the human fetal PPLT and IPLT suggests that this is fully functional and has a function comparable to peripheral lymph nodes.     

干燥综合征与粘膜相关型淋巴瘤临床病理分析

目的：探讨干燥综合征（ＳＳ）病理分析对诊断ＳＳ的意义、Ｍｉｋｕｌｉｃｚ病与粘膜相关淋巴组织（ＭＡＬＴ）型淋巴瘤的关系。方法：回顾性分析１５９例经病理证实的ＳＳ,对疑为ＭＡＬＴ型淋巴瘤的６例用免疫组化ＡＢＣ法标记,使用抗体ＬＣＡＬ－１、Ｌ２６及免疫球蛋白ＩｇＧ、ＩｇＡ、ＩｇＭ、ＩｇＤ、ＩｇＥ和к、λ。结果：６例可疑病例中有４例发生ＭＡＬＴ型淋巴组化ＬＣＡ、Ｌ２６、ｂｃｌ－２、ＩｇＭ、к和ＩｇＭ、λ呈     

A histological and immunocytochemical study of lymphoid tissue in rectal biopsies from homosexual men

A histological study of the lymphoid tissue of the rectums of 323 homosexual and 30 heterosexual men (including five intravenous drug users seropositive for human immunodeficiency virus, HIV) was undertaken. Marked lymphoid hyperplasia (germinal centre greater than 680 microns in diameter) was found in 13 men, nine of whom had a sexually transmitted infection of the rectum. Immunocytochemical studies showed that the germinal centres contained B-cells and follicular dendritic cells, surrounded by CD4+ and CD8+ T-cells in a ratio of between 5:1 and 10:1. In HIV-infected men there were decreased numbers of CD4+ cells and increased numbers of CD8+ cells, resulting in a ratio of between 0.8:1 and 2:1. In biopsies from four of seven HIV-infected men the follicular dendritic cell processes appeared shorter and fragmented. The pathogenesis of HIV infection is discussed in the light of these findings.     

黏膜相关淋巴组织淋巴瘤和凋亡相关基因

细胞凋亡受抑是黏膜相关淋巴组织(mucosa-associated lymphoid tissue, MALT)淋巴瘤发生的重要机制。MALT淋巴瘤凋亡相关基因的研究逐渐引起了重视。API2-MALT1融合基因和bcl-10过表达分别激活NF-κB,以NF-κB激活为核心,涉及到p53,Fas,API2,MALT1等凋亡相关基因,导致细胞凋亡受抑。     

Uptake of microparticles into the epithelium of human nasopharyngeal lymphoid tissue

The M cells of nasopharyngeal lymphoid tissue (NALT) have been considered to play an important role for vaccine delivery systems in humans. A number of investigations have reported particle uptake data in NALT of rodents. However, there have been no reports indicating any involvement of the nasopharyngeal lymphoid tissue in human vaccination. In the present study, we investigated whether the epithelium of human adenoid tissues might incorporate fluorescent microparticles using electron and fluorescent microscopy. The dissected adenoid tissues were incubated with various sizes and concentrations of fluorescent microparticles for 120 min at 37°C. Furthermore, the effect of surface coatings of microparticles with cations on the uptake into the epithelium of adenoid tissues was investigated. Transmission electron microscopy revealed that microparticles were taken up by the M cells of human nasopharyngeal lymphoid tissues. The NALT-M cells showed greater uptake of the smallest particles, 0.2 μm in diameter, than those of 0.5, 1.0, or 2.0 μm diameter. It was also revealed that surface coatings with poly-l-lysin or chitosan resulted in efficient uptake into the NALT. These results indicate that nasal administration of antigenic microparticles, which were coated with cationic materials, probably leads to a useful method of transnasal vaccination against respiratory and intestinal infections in humans.     

Benign lymphoid hyperplasia (pseudolymphoma) of soft tissue

Benign lymphoid hyperplasia (pseudolymphoma) has been reported in the skin, lungs, orbit, and gastrointestinal tract, but only rarely in soft tissues. These lesions mimic lymphoma both clinically and histologically. We describe a case of a pseudolymphoma of the deep soft tissues of the lower extremity. The lesion was composed of nonencapsulated lymphoid tissue with involvement of adjacent fat and connective tissues and multiple variably sized well-polarized germinal centers. Immunohistochemical staining, flow cytometry, chromogenic in situ hybridization for κ/λ light-chain restriction, and polymerase chain reaction for T- and B-cell gene rearrangements all revealed a polyclonal population of T and B cells, consistent with a benign reactive process. So far as we know, pseudolymphoma of the deep soft tissues has been described only once previously in the medical literature.     

Endometrial lymphoid tissue: an immunohistological study.

Lymphoid tissue of the endometrium was analysed by histological, immunohistological, and electron microscopical methods in 10 healthy uteri. A panel of monoclonal antibodies recognising macrophages (OKMI), HLA-DR antigen, B lymphocytes, T lymphocytes and their subsets, and dendritic reticulum cells was used in a two stage indirect immunoperoxidase labelling technique. Endometrial lymphoid tissue showed a remarkably consistent pattern of labelling in all cases. Lymphoid tissue was present in three sites: namely, (i) intraepithelial lymphocytes (predominantly T lymphocytes with occasional macrophages) associated with periglandular and sub-epithelial HLA-DR+, OKMI+ macrophages; (ii) interstitial lymphocytes and macrophages; (iii) lymphoid aggregates in the stratum basalis. These were composed mainly of T lymphocytes with a few B lymphocytes. Dendritic reticulum cells were found in those occasional lymphoid aggregates in which germinal centres were present. These features suggest that endometrial lymphoid tissue has many of the hallmarks of mucosal associated lymphoid tissue as found elsewhere in the body--for example, the bronchus and intestine. Endometrial lymphoid tissue appears to be unique, however, in that most of the stratum functionalis in which it is situated shows cyclical shedding during the menstrual cycle.     

Histological and immunohistological investigation of lymphoid tissue in the platypus (Ornithorhynchus anatinus)

The gross and histological appearance and the distribution of T and B lymphocytes and plasma cells are described for lymphoid tissues obtained from 15 platypuses. The spleen was bilobed and surrounded by a thick capsule of collagen, elastic fibres and little smooth muscle. White pulp was prominent and included germinal centres and periarterial lymphoid sheaths. Red pulp contained haematopoietic tissue. A thin lobulated thymus was located within the mediastinum overlying the heart. The cortex of lobules consisted of dense aggregates of small and medium lymphocytes, scattered macrophages and few reticular epithelial cells. In the medulla, Hassall's corpuscles were numerous, lymphocytes were small and less abundant, and reticular cells were more abundant than in the cortex. Lymphoid nodules scattered throughout loose connective tissue in cervical, pharyngeal, thoracic, mesenteric and pelvic sites measured 790±370 μm (mean±S.D. , n = 39) in diameter, the larger of which could be observed macroscopically. These consisted of single primary or secondary follicles supported by a framework of reticular fibres. Macrophages were common in the germinal centres. The platypus had a full range of gut-associated lymphoid tissue. No tonsils were observed macroscopically but histologically they consisted of submucosal follicles and intraepithelial lymphocytes. Peyer's patches were not observed macroscopically but histologically they consisted of several prominent submucosal secondary follicles in the antimesenteric wall of the intestine. Caecal lymphoid tissue consisted of numerous secondary follicles in the submucosa and densely packed lymphocytes in the lamina propria. Bronchus-associated lymphoid tissue was not observed macroscopically but was identified in 7 of 11 platypus lungs assessed histologically. Lymphoid cells were present as primary follicles associated with bronchi, as aggregates adjacent to blood vessels and as intraepithelial lymphocytes. The distribution of T lymphocytes, identified with antihuman CD3 and CD5, and B lymphocytes and plasma cells, identified with antihuman CD79a and CD79b and antiplatypus immunoglobulin, within lymphoid tissues in the platypus was similar to that described in therian mammals except for an apparent relative paucity of B lymphocytes. This study establishes that the platypus has a well-developed lymphoid system which is comparable in histological structure to that in therian mammals. It also confirms the distinctiveness of its peripheral lymphoid tissue, namely lymphoid nodules. Platypus lymphoid tissue has all the essential cell types, namely T and B lymphocytes and plasma cells, to mount an effective immune response against foreign antigens.     

Proliferation and differentiation of tumour cells from B-cell lymphoma of mucosa-associated lymphoid tissue in vitro

Several characteristics of lymphomas of mucosa-associated lymphoid tissue (MALT type) suggest that they are antigen-dependent and that their growth parodies a normal immune response. We have previously shown that three cases of low-grade B-cell MALT-type lymphoma recognize autoantigens. In this study, we investigated the response of three low-grade and one high-grade case of MALT-type lymphoma to anti-idiotypic antibody as a model of antigen binding either alone or as a co-stimulus with B-cell mitogens. We also studied the response of tumour cells to interleukin-6 (IL-6), which induces differentiation to immunoglobulin-producing cells in many systems. Of the four cases studied, one low-grade case showed markedly enhanced proliferation in response to anti-idiotype alone. This could not be increased by the addition of mitogens. In the remaining two low-grade cases, mitogen responsiveness was observed which was affected by anti-idiotype either by an enhancement or by a reduction in the proliferative response. The high-grade case failed to respond to the stimuli studied. No response to IL-6 was observed. This study supports the suggestion that antigen may affect the pathogenesis of low-grade tumours of MALT type.     

宫颈粘膜相关淋巴瘤及假性淋巴瘤临床病理和免疫组化研究

目的：探讨宫颈粘膜相关淋巴瘤（ＣＭＡＬＴ－ｏｍａ）及假性淋巴瘤（ＣＰＬ）的诊断标准、鉴别诊断及发病机理。方法：ＣＭＡＬＴ－ｏｍａ及ＣＰＬ各５例，活检或手术标本做石蜡切片及免疫组化（ＡＢＣ法）染色。结果：ＣＭＡＬＴ－ｏｍａ出现“淋巴上皮病变”及单克隆增殖，２例为Ｔ小多形细胞性，３例为Ｂ细胞性（ＣＣＬ和淋巴浆细胞型）。ＣＰＬ均有多克隆性的多种炎细胞浸润。结论：大多数ＭＡＬＴ－ｏｍａ为低度恶性并有“回归”现象。因此，手术为首选治疗方法。如果肿瘤侵犯邻近脏器或转移至淋巴结，应加用化疗或放疗。ＣＰＬ应予以有效的抗菌治疗，否则，有转变成ＭＡＬＴ－ｏｍａ的可能。自身免疫性疾病及感染，可导致机体产生获得性ＭＡＬＴ，并在持续性刺激下发展为ＣＰＬ，进而转变为ＣＭＡＬＴ－ｏｍａ。