Normal Thymic Development Research Articles

Characterization of stromal cell populations in the developing thymus of normal and nude mice.

The role of the thymic stromal components in T cell maturation has been investigated by compairing stromal composition in the developing thymus of normal mice with that of nude mice which are unable to support thymopoiesis. Stromal cell populations have been characterized using monoclonal antibody recognizing class II (Ia) major histocompatibility complex antigens, monoclonal antibody A2B5 recognizing GQ gangliosides characteristic of neuroendocrine cells and monoclonal antibody LE.61 recognizing a determinant associated with the tonofilaments of simple epithelia. Using these probes we have shown that the majority population of Ia+, LE.61+ cells is distinct from the A2B5+ stromal population and that both these populations appear early in normal thymus development showing a similar pattern in vivo and in thymus lobes developing in organ culture. In the nude thymic rudiment both Ia and LE.61 labeling are absent supporting previous conclusions on the epithelial nature of the thymic defect in these animals. In contrast, A2B5+ cells are present in the nude thymic rudiment indicating that these cells are unlikely to share the same developmental origin as the Ia+ epithelial population. In functional terms these results suggest that the Ia+ LE.61+ components, deficient in the nude mouse, are essential for normal thymus function and that whatever the function of the A2B5+ population, alone they are not sufficient to support thymocyte development.

Expression and function of major histocompatibiliby complex antigens in the developing thymus: studies on normal and nude mice.

Direct access of lymphoid precursors to the thymic environment appears to be an essential step in the differentiation of normal T cell populations and it is possible that intimate cellular interactions between T cells and the thymic stroma are involved in selective processes leading to self-tolerance and major histocompatibility complex (MHC) restriction. As an approach to investigating the intrathymic environment, MHC antigen expression during normal thymic development and lymphopoiesis, and in the embryonic thymus of T cell-deficient nude mice, has been examined. Evidence has been obtained to show that MHC antigens controlled by both the K and I regions are expressed from an early stage on epithelial cells in normal thymus development but that the thymic rudiment in nude mice shows a selective absence of I regions antigens. The implications of these findings for T cell development and the derivation and constitution of the intrathymic environment are considered.

Tissue interaction in the development of thymus lymphocytes.

Thymic rudiments from chick and mouse embryos have been cultured in diffusion chambers on the chick chorioallantois. In this situation their supply of blood-borne stem cells is cut off. Although rudiments from older embryos become fully lymphoid under these circumstances, primordia from early embryos fail to develop any lymphoid cells. Early chick rudiments will however develop completely if they are grafted directly to the chorioallantois where they receive a vascular supply. It is concluded that stem cells first enter the chick thymic anlage at between 6 and 7 days' incubation and the mouse thymic rudiment between 10 and 11 days' gestation. During the following few days of development there is a rapid inflow of stem cells to the rudiments. Since it is likely that stem cells, once they have entered the thymic primordium, are capable of only limited proliferation, it must be concluded that an inflow of stem cells continues once full lymphopoiesis has begun, although perhaps at a reduced rate. Finally, the importance of the interaction between stem cell and organ rudiment to normal thymic development is discussed in relation to the pathogenesis of thymic anomalies.

SENSORY DISTURBANCES OCCURRING IN SCIATICA DUE TO INTERVERTEBRAL DISC PROTRUSIONS: SOME OBSERVATIONS ON THE FIFTH LUMBAR AND FIRST SACRAL DERMATOMES

The lamin B receptor (LBR) is a highly unusual inner nuclear membrane protein with multiple functions. Reduced levels are associated with decreased neutrophil lobularity, whereas complete absence of LBR results in severe skeletal dysplasia and in utero/perinatal lethality. We describe a mouse pedigree, <i>Lym3</i>, with normal bone marrow and thymic development but profound and progressive lymphopenia particularly within the T cell compartment. This defect arises from a point mutation within the <i>Lbr</i> gene with only trace mutant protein detectable in homozygotes, albeit sufficient for normal development. Reduced T cell homeostatic proliferative potential and life span in vivo were found to contribute to lymphopenia. To investigate the role of LBR in gene silencing in hematopoietic cells, we examined gene expression in wild-type and mutant lymph node CD8 T cells and bone marrow neutrophils. Although LBR deficiency had a very mild impact on gene expression overall, for common genes differentially expressed in both LBR-deficient CD8 T cells and neutrophils, gene upregulation prevailed, supporting a role for LBR in their suppression. In summary, this study demonstrates that LBR deficiency affects not only nuclear architecture but also proliferation, cell viability, and gene expression of hematopoietic cells.