The Hassalľs Bodies

Abstract

During the 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 RE cells, which usually undergo hypertrophy prior to their inclusion in the outer cell layer of the corpuscles. In our observations 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. 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 antibodies (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 thymic RE cell surface antigens, 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 in human skin, 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. We also observed the expression of transforming growth factor-β type II receptors in HBs. The recently detected expression of the homeobox gene products B3, B4, and C6, transcription factors involved in developmental processes related to hematopoiesis within HBs provides further evidence that HBs are important functional components of the RE network of the thymus which provide developing thymocytes with paracrine and juxtacrine signals to ensure their proper functional maturation during the intrathymic lymphopoiesis. Our transmission electron microscopical (TEM) studies on HBs determined the existence of groups of RE cells connected to one another by desmosomes. We went on to further observe 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 electron microscopy (SEM). 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. Future immunohistochemical and genetic studies will clarify the exact origin of the various non-lymphatic thymic cells participating in the determination of the particular physiological activities, progressive growth, and the terminal cell differentiation within the HBs.Key wordsThymic Ontogenesis in VertebratesOrigin of the Hassalľs Bodies (HBs)—HypothesesReticulo-Epithelial Cell Origin of HBsCapillary InvolvementMorphological ObservationsScanning Electron microscope (SEM) StudyTransmission Electron microscope (TEM) ObservationImmunocytochemistryStreptavidin-biotin antigen detection techniqueMouse Anti-Human Monoclonal Antibody (MoAB)Immunophenotype (IP)Thymic Organ and Tissue CulturesTotal Body and Local Thymic IrradiationThymic involution