[Immunohistochemical analysis of splenic tissue in rats with destruction of the hypothalamic structures]. / Immunogistokhimicheskii analiz selezenochnoi tkani u krys s razrusheniem gipotalamicheskikh struktur.

The immunoenzyme histochemical technique to stain the IgM- and IgD-bearing cells was used to study the morphometric characteristics of B-lymphocyte-dependent zones in spleen white pulp of Wistar rats (intact, sham operated and after cortex or hypothalamic lesions). In the groups of sham-operated and cortex-lesioned rats it has been shown the increase of spleen weight 7 days after the operation due to the increase of the red pulp weight. The white pulp compartment's ratio is not affected. Lesioning of the posterior hypothalamic area prevents these effects of the operation, while local coagulation of the lateral hypothalamic area causes a significant decrease of the weight of spleen primary follicules which contain IgM+IgD+-bearing B-lymphocytes exerting characteristics of circulating pool of B-lymphocytes. These data are in favour of the CNS participation in regulation of B-lymphocyte migratory activity.

Failure to detect immune deficiency in rats after prenatal or early postnatal irradiation.

We have looked for medium-term sequelae in the immune system of rats that had been X-irradiated (0-2 Gy whole-body irradiation) during prenatal or early postnatal life. At an age of 8 weeks the histology of the spleen was normal, and so was the distribution of B and T lymphocytes. The serum immunoglobulin levels were not significantly altered, even when the different isotypes were considered. At an age of 10 weeks, the rats were immunized with a T-dependent or a T-independent dinitrophenylated-carrier antigen. Normal levels of specific antibodies were generated in all groups of animals injected with the T-independent antigen. The T-dependent response, in contrast, was higher in animals irradiated between day 6 and day 20 of gestation (but not in rats irradiated early after birth). This increase, however, was significant only for the IgM and IgG1 responses of some irradiated groups. Thus no medium-term immunodeficiency could be documented with the methods used. The alteration in a T-dependent response, however, points to a radiosensitive T regulatory mechanism.

Lymphocyte disappearance and reappearance after a single whole-body irradiation dose of 5 Gy.

The effects of a single exposure to 5 Grays of caesium gamma rays administered at a high-dose rate were investigated in rat lymphocyte populations. Such a dose completely depleted the B-cell population but never totally depleted the T-cell population. T and B lymphocytes reappeared in the spleen after 10-15 days and somewhat later in the mesenteric lymph nodes and Peyer's patches. In the spleen, non-circulating B lymphocytes of the marginal zone reappeared after a few days, as did the B lymphocytes of the follicles. Lymphoid tissues were observed to have recovered their normal aspect between days 50 and 60 after irradiation; however, even at that time, the germinal centres had not yet returned to normal.

Studies of long-term continuous irradiations using daily doses ranging from 0.07 to 0.30 Gy on the B lymphoid system of the rat.

The effects of a continuous exposure to cobalt gamma rays administered to rats at a daily dose of 0, 0.07, 0.12, 0.20 or 0.30 Gy for a period of up to 90 or 135 days, have been observed on their B lymphocyte populations and on their immunoglobulin serum levels. The effects increase with the daily dose and the duration of irradiation. At a daily dose of 0.07 Gy, no clear effect was observed. The depletion was almost negligible after 30 days at a daily dose of 0.12 Gy, but visible after all other doses and durations. However, a clear difference in susceptibility was observed between the marginal zone B compartment and the follicular one, the former being much more affected by the radiation than the second.

B-cell production and differentiation in adult rats.

The B-cell development in a group of rats was suppressed for the first 45 days of life by serial administration of rabbit anti-rat IgM and IgD antibody. Total or near total suppression of B lymphopoiesis was achieved. At 45 days, suppression was stopped by injection of IgM and IgD rat paraproteins. The sequence of B-cell and plasma cell development following suppression was assessed by immunohistological analysis of spleen lymph nodes and small intestinal lamina propria. The main findings are listed below. Complete reconstitution of B-cell numbers occurs within 8 days, at which stage germinal centres are also present. B lymphopoiesis in the red pulp of the spleen differs from that reported for bone marrow. Cells develop expressing surface sIgM and sIgM with IgA, but not sIgD. sIgD-positive cells first appear in splenic follicles 2 days after stopping suppression, but their appearance in lymph nodes is delayed until after 3 days. At this stage, sIgD-positive cells become apparent in the splenic red pulp. IgM plasma cells appear from day 4. IgA plasma cells in the gut appear in small numbers at day 6, and gradually increase to normal numbers by day 14. sIgG2c expression in the splenic marginal zone did not approach normal levels, even 2 weeks after suppression was stopped.

The specific IgM response in rats genetically selected for high or low serum IgM level.

The IgM response to SRBC in a line of rats selected for high serum IgM was higher and lasted longer than that in a line of rats selected for low IgM, while the response to TNP-LPS was similar at its peak in the two lines but persisted longer in the 'high' line. The difference between the lines is therefore more likely to be at the macrophage and/or the T cell level than at the B cell level.

Immunohistological observations on the spleen B lymphocyte populations from whole-body irradiated rats.

The effects of a single exposure to caesium gamma rays administered to rats at high dose rate have been observed on their spleen B lymphocyte populations. These effects increase with the dose as well as with the time, at least within the following ranges of experimental conditions: from 0 to 12 Gy and observation times of 1 and 3 days after irradiation. Doses less than or equal to 1.50 Gy lead to only a slight reduction of the B lymphocyte populations. On the contrary, doses equal to or greater than 3.50 Gy are extremely destructive for the spleen B lymphocytes. The non-circulating B lymphocyte population of the marginal zone compartment seems more susceptible to ionizing radiations than the circulating B lymphocyte population of the follicular compartment.

Genetic regulation of immunoglobulin synthesis: selection of two rats' lines with respectively a high or low IgM serum level.

Two directional selections of rats for a high or a low IgM serum levels have been carried out. The criterium of selection was the individual merit of each rat in having a high or a low IgM level when they were 3 months old. All animals were kept together, in order to avoid external influence on the IgM synthesis. The founding population was a mixed nucleus of rats, obtained by breeding of 13 different strains of inbred or outbred rats for two generations. Two lines, one with a high IgM serum level and another with a low IgM serum level, have been separated. At generation 10, they differed from each other by a coefficient of approximately four. These IgM serum levels were not due to differences in IgM catabolism of the two lines since both lines had similar IgM half-lives. Analyses of the data obtained show that, for IgM synthesis, the coefficient of heritability varies between 0.30 to 0.40, and the number of 'independent loci' controlling IgM synthesis ranges from 11 to 14.

The non-specific enhancement of allergy. I. In vivo effects of Bordetella pertussis vaccine on IgE synthesis.

Bordetella pertussis organisms, with or without a small dose of alumhydroxide, enhance in rats the production of IgE antibodies to an unrelated antigen, even if this antigen has been administered 6 weeks beforehand. This non-specific enhancement of IgE antibodies is accompanied by a substantial rise in total serum IgE and by the production of IgE antibodies to B. pertussis. The effect of B. pertussis on IgE synthesis is dose-dependent. No effect of B. pertussis on IgE production can be observed in nude rats.

[Pathogenesis of post-irradiation infection. 2. Role of polynucleated neutrophils in the defense of irradiated rats against Yersinia enterocolitica]. / Pathogénie des infections après irradiation. 2. Rôle des polynucléaires neutrophiles dans la défense des rats irradiés contre Yersinia enterocolitica.

Wistar R inbred rats showed a substantial mortality when they were given Yersinia enterocolitica eight days after a 6.5 Gy total body irradiation. The possibility to abolish the high susceptibility of these irradiated rats to Yersinia enterocolitica by intravenous injections of isogenic neutrophils is presented: irradiated rats injected with 7 to 10.10(7) isogenic neutrophils, by the intravenous route, just before or after the administration of Yersinia enterocolitica, were not susceptible. On the contrary, control irradiated rats, not transfused, were killed by the same bacterial challenge.

Pathogenesis of post-irradiation infections. I. Yersinia enterocolitica administered to normal and irradiated rats.

Infections after irradiation can be due to a great variety of microorganisms many of which are normally non-pathogenic or conditionally pathogenic for the host. The strain of Y. enterocolitica used was not pathogenic to a variety of unirradiated rats nor to athymic or B lymphocyte deprived, macrophage depleted rats, nor to normal rats irradiated by 5.7 Gy 24 hours before. However similarly irradiated rats receiving Y. enterocolitica 5 to 10 days later showed a substantial mortality. It is concluded that the radiosensitive mechanism for protection against Y. enterocolitica is not humoral nor cellular immunity as mediated by T and B lymphocytes or macrophages.

Influence of adrenergic drugs on IgE production.

The influence of some adrenergic drugs (fenoterol, salbutamol, terbutaline as stimulant; propranolol as blocker) on IgE production in the rat was investigated. The drugs were administered orally, mixed in the food. The stimulant drugs caused a significant decrease of total serum IgE but had no influence on the specific IgE antibody response. The beta adrenergic blocker caused a significant increase of total serum IgE but also had no influence on specific IgE. The effect of terbutaline was blocked by propranolol. No influence of these adrenergic drugs on IgA and IgM levels was observed.

Immunoglobulin production in nude rats with special attention to the IgE isotype.

The production of immunoglobulins has been studied in Nude (rnu/rnu) rats as well as in their controls (RNU/+). A prototype of humoral T-dependent immune response, the anti-DNP-OVO reaginic production was found very low in Nude rats by comparison to their controls. The percentage of Ig-bearing cells in mesenteric lymph nodes was increased to about the double of those of the control. This percentage can be explained by the absence or at least the great depletion of the thymus derived lymphocytes. On the contrary, the Ig serum levels were rather normal and could correspond to T-independent antigenic stimulation and to membrane immunoglobulin shedding, at least for the IgE isotype.