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Biomedical subjects

F Loor

Publications and source records attributed to F Loor.

At least 91 records · Page 5Linked to original sources

The C57BL/6 nu/nu lpr/lpr mouse. I. Expression of the 'lpr phenotype' in the C57BL/6 genetic background.

The C57BL/6 lpr/lpr mice develop within 3-6 moths a series of abnormalities of their immune system which characterize the 'lpr phenotype' and allow them to be distinguished easily from normal C57BL/6 as well as from C57BL/6 nu/nu: lymphadenopathy, hyperimmunoglobulinemia, high anti-nuclear antibody titers and, less regularly, anti-whole DNA antibody. Though C57BL/6 nu/nu occasionally present auto-antibody too, the combined use of three or four of the aforementioned parameters for each tested animal allows an easy detection of animals presenting the lpr phenotype. In our C57BL/6 lpr/lpr colony, the lymphadenopathy does not seem to start by chance in any lymphoid organ but shows a very strong preferential occurrence in the cervical lymph nodes. These parameters of the lpr phenotype have been used to trace the lpr genes and to construct the C57BL/6 nu/nu lpr/lpr as described in the companion paper.

Animals↗

The C57BL/6 nu/nu lpr/lpr mouse. II. Pedigree and preliminary characteristics.

A short-cut procedure is described which allows to construct new mouse strains which are double congenic for the nu gene (nude, athymic) and the lpr gene (lymphoproliferation). Since both nu and lpr genes are recessive and that the lack of thymus impairs the expression of the lpr phenotype in euthymic animals, the homozygosity of nude animals for the lpr gene was based on the results of progeny analyses. A C57BL/6 nu/nu lpr/lpr (B6 nu/nu, lpr/lpr) was made in four generations starting from C57BL/6 nu/nu (B6 nu/nu) and C57BL/6 lpr/lpr (B6 lpr/lpr). This possibility stems from an absence of close linkage of the nu and lpr genes. The emergence of the nude phenotype at the different steps of the pedigree was less frequent than expected if the nu and lpr genes were completely independent. However, this is probably due to environmental factors causing a negative selection of nude littermates. The B6 nu/nu lpr/lpr represents a new important tool for the study of how the thymus modulates the lpr gene controlled acceleration of autoimmunity. Preliminary data indicate that the lpr phenotype (massive lymphadenopathy and splenomegaly accompanied by severe auto-immune disease with features of systemic lupus erythematosus) appears when a thymus is grafted to the B6 nu/nu lpr/lpr.

Animals↗

Interference of cyclosporin with lymphocyte activation maintenance of the cells in a non-cycling phase and with a low intracellular pH.

Cyclosporin can block T cell activation by mitogens as evidenced by inhibition of exogenous thymidine integration into DNA and by blockage of the cells in the G0/G1 phase of the cell cycle. The mitogenic activation sequence shows at least one cyclosporin sensitive step at or prior to the rise of cytoplasmic pH (pHi), which normally occurs after exposure to mitogen and which seems to be a permissive condition for initiation of DNA synthesis (S phase of the cell cycle).

Animals↗

Interference of cyclosporin with lymphocyte activation: blockage of the mitogen-induced increases of lysosomal and mitochondrial activities.

Mouse lymphocytes were activated by a mitogenic dose of concanavalin A and analysed by flow cytometry to monitor the increases of mitochondrial activity (using rhodamine 123 as probe) and of lysosomal activity (using euchrysin [acridine orange] as probe). Cyclosporin A-treated lymphocytes were not capable of responding to concanavalin A in the same way as untreated lymphocytes: both the increased uptakes of rhodamine 123 by mitochondria and of acridine orange by lysosomes were strongly diminished, though not abolished. Cyclosporin may thus interfere at a step of activation prior or concurrent to those early changes of lymphocyte physiology. It looks like that it allows mitogen-activated cells to go through part of the mitochondrial maturation which precedes initiation of nuclear DNA synthesis, after which the cells remain blocked at that incomplete maturation level.

Acridine Orange↗

Cytoplasmic lipid droplets as the possible eventual cellular fate of active forms of cyclosporin.

The activity of cyclosporins can be defined with regard to their ability to inhibit the proliferation of susceptible lymphoblastoid cell clones. All active cyclosporins cause the emergence of highly refringent globular bodies, independently of cell susceptibility to cyclosporin. Cyclosporins devoid of proliferation-inhibition capability do not cause such alterations in cell morphology. The use of dansylated active cyclosporins suggests that within a few hours of treatment in vitro, most if not all cyclosporin is contained within those globular bodies. By using cytochemical methods allowing differential staining, we show here that these cyclosporin-containing structures are neither normal mitochondria (shown by use of rhodamine 123) nor normal lysosomes (shown by use of acridine orange under stringent staining conditions) but most probably lipid droplets (shown by use of perylene and various dansylated hydrophobic probes).

Animals↗

Selective migration of 'null' cells towards a thymus factor in vitro.

Mouse fetal liver, nude adult bone-marrow and normal adult bone-marrow cells are depleted of theta+, Ig+ cells by the use of in vitro migration through a porous membrane towards a thymus supernatant attractant. The attracted cells are free in suspension, viable and can be obtained in large numbers through the use of multiple migration wells for in vivo testing.

Animals↗

Capping revisited. I. Inhibition by some thiols.

The capping, but not the clustering (spotting), of membrane immunoglobulins and of other lymphocyte membrane macromolecules is inhibited when the medium contains some reducing agents, principally cysteine. The inhibition is easily reversible, being rather a retardation of capping than its blockage. The mechanism of inhibition is still unclear, but it definitely depends on the sulfhydryl moiety of the thiols.

Amino Acids↗

Mouse thymus reticulo-epithelial (RE) cells in vitro: isolation cultivation and preliminary characterization.

The reticulo-epithelial (RE) cells of the thymus are presumably playing a crucial role in the differentiation of the T lineage lymphoid cells, but how this happens is still a matter for speculation. This paper describes a method for rapid preparation of thymic RE cells with as little damage as possible, their culture, and the analysis of their membrane antigens and of other cytological properties. The cultured cells are pleiomorphic, but at least two types can be distinguished, one being round and very villous, the other one being flat and very cystic. Thymus RE cells have species specific surface antigens and large amounts of H-2 antigen. The possible presence of theta antigen is unclear. Most cells have no detectable Tla antigen. In vitro, they show some uptake of normal mouse serum immunoglobulins. RE cells show a surface migration of ligand-bound membrane antigen; such a capping is much slower than for lymphocytes, and is inhibited by 10 mM NaN3; The drug also causes the apparition of long microprojections (or retraction fibres) on the villous RE cell type, as is also caused by a slight fixation with formalin. Type C virus particles are found in RE cells from AKR mice as young as 1 day.

Animals↗

Switch in immunoglobulin class production observed in single clones of committed lymphocytes.

Mouse spleen cells, after stimulation with lipopolysaccharide, were cloned in culture. After 4 to 5 days, the daughter cells were stained and examined for immunoglobulin class with double immunofluorescent reagents. A switch of the stained color of these cells was observed, implying a switch from imunoglobulin M to immunoglobulin G production in the progeny of a single B cell.

Animals↗

Allelic exclusion in the B lineage cells of the rabbit.

Allelic exclusion of the K polypeptide chain allotypes b4 and b5 of the rabbit exists for the immunoglobulins of almost all plasma cells and of most mature small B lymphocytes. However, both these alleles are expressed simultaneously in rare plasma cells and in an usually large fraction of the lymphoid cells of the bone marrow. Our experiments support the idea that such bone marrow B lineage cells do not always show allelic exclusion.

Alleles↗

Maternal allotype dominance and allelic exclusion in the B lineage cells of the newborn rabbit.

Newborn rabbits from parents which differ at the b allotype locus (kappa chain), show a strong maternal allotype dominance, especially in the bone marrow. This concerns not only the membrane but also the cytoplasm, and it cannot be simply due to a passive uptake of maternal immunoglobulins. The spleen precedes the bone marrow for a high level of expression of the paternal allotype. In the thymus, cells which contain cytoplasmic immunoglobulin are found at low frequency, but their absolute number represent a substantial contribution to the B lineage cell pool. A small proportion of such thymus cells do not show allelic exclusion of kappa chain allotypes.

Alleles↗

Restoration of the T lymphoid system of nude mice: different regeneration of neonatal and adult thymuses.

When a neonatal thymus and an adult (reticuloepithelial) thymus from normal mice are simultaneously grafted to individual adult nude mice, the host-derived T cell precursors regenerate the neonatal thymus more efficiently than the adult (reticuloepithelial) thymus. Thus, this is a direct cause for the poor restoration of the T lymphoid system of nude mice by adult and/or reticuloepithelial thymus grafts.

Aging↗