Bodey B, Kaiser H E
Department of Pathology, School of Medicine, University of Southern California, Los Angeles, USA.
In Vivo. 1997 Jan-Feb;11(1):61-85.
The histogenesis and cell structure progression of Hassall's bodies (HB) was observed employing light and electronmicroscopic histochemical methods in 212 human and 100 dog fetuses at various stages of ontogenesis. Several human pre- and postnatal thymuses were investigated immunohistochemically, employing a library of over 50 poly- and monoclonal antibodies, seeking to determine the cell origin of HBs. The organization of optimal microenvironmental conditions in the thymus requires the added participation of the neural crest. Spontaneous or experimental ablation of the neural crest during early ontogenesis results in abnormal thymic organogenesis. The reticulo-epithelial (RE) cells of 25 postnatal thymuses were also observed under various tissue culture conditions. The development of the first HB was detected on the 38th day of gestation in dogs and during the second part of the third intrauterine lunar month in human fetuses. The greatest developmental progression and main cell-tissue organization of the HBs was observed between 45 and 54 days of gestation in dogs and between 6 and 10 lunar months in humans. During thymic ontogenesis, the HBs appear when lymphopoiesis is already established and the cortex, medulla and the cortico-medullary junction are capable of conducting the positive and negative selection of T lymphocytes undergoing progressive maturation. The HBs are structurally organized from medullary RE cells, which usually undergo hypertrophy prior to their inclusion in the outer cell layer of the corpuscles. The cellular microenvironment of the thymic medulla is composed of networks of cell types, of a variety of origins, and all of them may participate in the construction of growing, progressive HBs. Histochemically, we detected a rich content of basic non-histone proteins, PAS positive substance (glycogen and acid mucopolysaccharides within the bodies. Employing the histological stain of Pasini and immunocytochemical methods with monoclonal antidodies (MoABs) AE2 and AE3, high molecular weight (56.5 to 67 kD) basic keratins were defined in human HBs. Employing a panel of MoABs developed against epithelial cell surface antigens (provided kindly by Dr. Haynes), we observed immunoreactivity localized to the outer cell layer of the HBs with MoABs TE8, TE16 and TE19, while the centrally located cells reacted positively with TE15 and TE19. Immunoreactivity employing the TE8, TE16 and TE19 MoABs was also observed in the epidermal granulosa cell layer, while TE15 reacted with cells of the stratum corneum. The presence of endocrine, peptide secreting RE cells within the HBs was defined with the use of MoAB A2B5, which binds to the GQ ganglioside. The hypertrophied, physiologically active RE cells of the peripheral cell layer of the HBs reacted positively with medium to strong intensity when stained with MoABs UJ127.11, J1153, A2B5, 215.D11, and 275.G7. These results further suggest that HBs are not exclusively degenerative structures. Our transmission electronmicroscopical (TEM) studies on HBs determined the existence of groups of RE cells connected to one another by desmosomes. We also observed long cytoplasmic processes originating from medullary RE cells and directly contacting thymic T lymphocytes and accessory antigen presenting cells (macrophages, dendritic cells, interdigitating cells, Langerhans cells, etc.) by the use of scanning electronmicroscopy (SEM). During our observations on human thymic organ and tissue cultures, no development of HBs could be registered. It is possible that additional cell to cell interactions with cells of different derivations may be necessary for the development of HBs. Thus, our results indicate that the HBs are unique, antigenically distinct, functionally active, multicellular components of the nonlymphocytic, cellular microenvironment of the thymic medulla, and participate in the physiological activities of the prenatal and adult thymus.(ABSTRACT TRUNCATED)
运用光镜和电镜组织化学方法，在212例不同发育阶段的人胎儿和100例犬胎儿中观察了哈氏小体（HB）的组织发生和细胞结构演变。使用50多种多克隆和单克隆抗体库，对几例人出生前后的胸腺进行了免疫组织化学研究，以确定HB的细胞起源。胸腺中最佳微环境条件的形成需要神经嵴的额外参与。在早期发育过程中，自发或实验性切除神经嵴会导致胸腺器官发生异常。还在各种组织培养条件下观察了25例出生后胸腺的网状上皮（RE）细胞。在犬妊娠第38天以及人胎儿子宫内第三个农历月的后半期检测到首个HB的发育。在犬妊娠45至54天以及人妊娠6至10个农历月之间观察到HB的最大发育进程和主要细胞组织结构。在胸腺发育过程中，当淋巴细胞生成已经建立且皮质、髓质和皮质 - 髓质交界处能够对逐渐成熟的T淋巴细胞进行阳性和阴性选择时，HB出现。HB由髓质RE细胞构成结构组织，这些细胞在被纳入小体的外层细胞之前通常会肥大。胸腺髓质的细胞微环境由多种起源的细胞类型网络组成，它们都可能参与生长中的、逐渐发育的HB的构建。组织化学检测发现，小体内富含碱性非组蛋白、PAS阳性物质（糖原和酸性粘多糖）。运用帕西尼组织学染色法以及使用单克隆抗体（MoABs）AE2和AE3的免疫细胞化学方法，在人HB中确定了高分子量（56.5至67 kD）的碱性角蛋白。使用针对上皮细胞表面抗原开发的一组MoABs（由海恩斯博士惠赠），我们观察到MoABs TE8、TE16和TE19的免疫反应定位于HB的外层细胞，而位于中央的细胞与TE15和TE19呈阳性反应。在表皮颗粒细胞层也观察到使用TE8、TE16和TE19 MoABs的免疫反应，而TE15与角质层细胞反应。使用与GQ神经节苷脂结合的MoAB A2B5确定了HB内存在内分泌、分泌肽的RE细胞。当用MoABs UJ127.11、J1153、A2B5、215.D11和275.G7染色时，HB外周细胞层肥大、生理活性的RE细胞呈中度至强阳性反应。这些结果进一步表明HB并非仅仅是退化性结构。我们对HB的透射电子显微镜（TEM）研究确定存在通过桥粒相互连接的RE细胞群。我们还通过扫描电子显微镜（SEM）观察到源自髓质RE细胞的长细胞质突起，它们直接与胸腺T淋巴细胞和辅助抗原呈递细胞（巨噬细胞、树突状细胞、交错突细胞、朗格汉斯细胞等）接触。在我们对人胸腺器官和组织培养的观察中，未记录到HB的发育。对于HB的发育，可能需要与不同来源的细胞进行额外的细胞间相互作用。因此，我们的结果表明，HB是胸腺髓质非淋巴细胞性细胞微环境中独特的、抗原性不同的、功能活跃的多细胞成分，并参与产前和成年胸腺的生理活动。（摘要截选）
