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Biomedical subjects

B Cinader

Publications and source records attributed to B Cinader.

At least 91 records · Page 5Linked to original sources

Mitotic response of rabbit peripheral blood lymphocytes to a factor in normal rabbit serum: a possible genetic polymorphism.

Normal rabbit sera contain a mitogen capable of stimulating rabbit peripheral blood lymphocytes in in vivo culture to incorporate radioactive thymidine. Cells from spleen, appendix or peritoneal exudate did not respond when cultured under similar conditions. The responding peripheral blood lymphocytes are adherent cells, but not macrophages. Presence of responding peripheral blood lymphocytes is a dominant trait. The response is regulated by a nonadherent, radiation-sensitive suppressor cell and by a nonadherent, relatively radiation-resistant helper cell.

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Resistance of MRL/Mp-lpr/lpr mice to tolerance induction.

Mice of strain MRL/Mp-lpr/lpr develop resistance against tolerance induction with aggregate-freed rabbit gamma-globulin as early as 6 weeks of age and show very complete resistance when they are 10 weeks old; congenic mice MRL-Mp+/+ of 6 and 10 weeks can be rendered tolerant. By reconstitution experiments, it was shown that T cells from MRL/Mp-lpr/lpr are responsible for the resistance to tolerance induction. A cell which is not colchicine-sensitive contributes to tolerance of MRL/Mp-+/+, but not to MRL/Mp-lpr/lpr mice. Resistance of T cells against tolerance depends on expression of the lpr gene.

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Diversity of age-dependent changes of antibody formation and of tolerance decrease.

Age-dependent changes in immune response and in tolerance occur at different rates in inbred mice of different genetic backgrounds. The change in tolerizability is connected with the change in the balance of the suppressor helper circuit; the change in B-cells, at least in C57BL/6 mice, appears to be also due to a regulatory change. Changes in immune responsiveness and tolerance inducibility appear to vary independently of one another.

Aging↗

Relative expression of light-chain allotypic specificities on the surface of rabbit lymphocytes as a function of age.

Lymphoid cells of heterozygous Ab4/Ab9 rabbits of various ages were stained with fluorescent anti-allotype antibodies. In foetal and newborn rabbits, the percentage of Ab-positive cells in low; it increases with age, reaching the adult value when the animals are 100 days old. The rate of increase in the percentage of Ab4-positive cells is higher than in that of Ab9-positive cells. Thus, the Ab4/Ab9 ratio, which is initially 1, increases with age and reaches 2.2. in spleen and 4 in appendix of young adult animals. We conclude that the change in Ab4/Ab9 ratio is due to differential clonal expansion which we attribute to charge-related differences in the ability of Ab4 and Ab9 receptor-bearing cells to capture antigen when environmental antigens are encountered in postnatal life.

Aging↗

Age-dependent separation of class-specific suppressor cells in thymus of SJL/J mice.

The thymus of SJL/J mice of age 3-6 weeks has been previously shown to contain suppressor cells that inhibit the antibody response to lymph node cells to SRBC. The effect of these suppressor cells disappear as the animals age (24 weeks or more). We find that these aged animals acquire thymic suppressor cells which suppress the generation of cytotoxic T-cells both in vitro and in vivo. Although such suppressors are not present in the thymuses of young SJL/J mice, suppression can be induced by treatment with estrogen and progesterone. The differentiation of functionally different suppressor cell populations in thymus may be affected by both age and hormonal status.

Aging↗

Accelerated age-dependent decline in the T suppressor capacity of SJL mice.

Tolerance induction with rabbit gamma-globulin was employed as a probe for age-dependent changes in suppressor capacity of SJL lymphoid cells. The tolerant state was assessed by loss of cooperative capacity and by infectious tolerance. The supply of precursor cells was assessed by thymectomy and by treatment with colchicine and cyclophosphamide, which have been reported to eliminate suppressor cells. Thymectomy, 16-18 days before tolerance induction, did not affect antibody response or tolerance inducibility; thymectomy, 33 days before tolerance induction, reduced both antibody response and tolerance inducibility. Colchicine, injected together with aggregate-freed rabbit gamma-globulin, inhibited tolerance induction partially in 35-day-old mice and completely in 106-day-old mice. Colchicine, given to younger mice, thymectomized 17 days before tolerance induction, prevented tolerance induction completely. A low dose of cyclophosphamide interfered with tolerance induction in older, but not in younger mice. A high dose of cyclophosphamide interfered with tolerance induction in thymus cells of younger and older mice. After thymectomy, there was a much more profound interference of a low dose of cyclophosphamide with tolerance induction. Results were discussed in terms of an age-dependent decline of thymus progenitors and of peripheral progenitors of suppressor cells.

Aging↗

The effect of temperature-dependent autorosettes on B/T cell ratios of purified rabbit peripheral blood lymphocytes.

Contradictory reports as to B/T cell ratios in the peripheral blood lymphocytes (PBL) of rabbits led to an investigation of current purification methods. PBL prepared by sedimentation at 37 degrees C in gelatin solution showed the same B/T ratios as did whole blood. PBL prepared by the Ficoll-Hypaque method at 4 degrees C or at room temperature were enriched in B cells compared to the whole blood. This enrichment depended on the presence of autologous erythrocytes during centrifugation and it was not demonstrable when centrifugation was carried out at 37 degrees C. Resuspended red cell pellets contained more than 3 times as many rosette-forming cells if the pellets were obtained by centrifugation of blood on Ficoll at 4 degrees C rather than 37 degrees C. We, therefore, conclude that aggregation of T cells with autologous erythrocytes is responsible for the depletion of B cells in the PBL prepared by the Ficoll-Hypaque method at 4 degrees C or at room temperature.

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Effect of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) on tolerance induction in SJL mice.

The effect of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) on tolerance induction with rabbit gamma globulin (RGG) was investigated. The treatment with ribavirin, initiated on the 4th and 17th day of life, did not reduce the immune response significantly, but provided a much more profound level of tolerance than could be achieved in animals not treated with ribavirin. When treatment with ribavirin was initiated at the age of 50 or 65 days, the response of immunized animals was reduced and the response of tolerized-immunized animals was increased. The mechanism, underlying the drug action, was discussed in terms of an effect or ribavirin on the balance between help and suppression; the possibility that a virus may be involved in age-dependent changes and that ribavirin prevents it proliferation, was considered.

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Suppressor cells and their precursors in A/J mice, tolerant to heterologous gamma globulin.

The role of suppressor cells and of their precursors was examined in A/J mice, immunized or tolerized-immunized with rabbit gamma globulin. Antibody response and tolerance were assessed by antigen elimination, followed by an indirect plaque-forming assay. Reconstitution experiments were performed to estimate loss of cooperative capacity in thymus and spleen cells. Infectious tolerance was examined by reconstitution with mixtures of spleen or thymus cells of normal and tolerant donors. Infectious tolerance could not be detected after neonatally induced tolerance. It could be detected when tolerance was induced 11-16 days after birth. Under these circumstances, loss of cooperative capacity and increased capacity for infectious tolerance occurred rapidly over the first 2 days and reached completion by the 10th-20th day after administration of tolerogen. Thymectomy, after tolerance induction, resulted in relative recovery of responsiveness of spleen cells and loss of capacity for infectious tolerance. Pretreatment with cyclophosphamide resulted in a less profound state of unresponsiveness and in the disappearance of the capacity for infectious tolerance. Simultaneous treatment with tolerogen and colchicine also resulted in a less profound state of tolerance. This effect of colchicine was more profound when a low dose of tolerogen was used or when animals were thymectomized before administration of tolerogen and colchicine.

Animals↗

A strain survey of age-dependent changes in antigen elimination, antibody formation and tolerance.

A strain survey has been undertaken to examine polymorphism of age-dependent changes in antigen elimination, immune responsiveness and tolerance inducibility. In young mice of tested strains, other than C57BL/6J, aggregate-freed mouse Ig was eliminated faster than was the xenogeneic Ig(RGG); C57BL/6J was the only exception. The rate of elimination increased with age in all strains, tested. Antibody formation to RGG decreased in 3 (BALB/cJ, 129/J, DBA/2J) out of the eleven strains tested at 5--7 and 31--40 weeks of age; there was a considerable strain variation in the extent of this decrease. Age-dependent resistance to tolerance induction was observed in a fraction of animals of H-2 haplotypes, H-2k and H-2d.

Aging↗

Isolation and characterization of a mouse-rabbit hybridoma.

Immunoglobulin was obtained from a hybridoma cell line, which was a reclone of a hybrid between a rabbit cell and mouse myeloma cell (X63-Ag8). The immunoglobulin, isolated from the cell culture medium was found to be homogeneous by isoelectrofocusing and immunoelectrophoresis and consisted of mouse heavy and rabbit light chains, linked by disulphide bonds. All immunoglobulin molecules carried both mouse and rabbit determinants; mouse determinants were associated only with the heavy chains while rabbit determinants were only associated with the light chains. The rabbit light chains were of Ab4 allotypical specificity, but possess only some of the Ab4 determinants normally present in Ab4/Ab4 animals. It was suggested that the restriction in allotypical specificity may be a general property of light chain Ab allotypes; the normal serum immunoglobulins may be heterogeneous with respect to the allotypic determinants and any one molecule may possess only a proportion of determinants detected by a conventional anti-allotype antiserum.

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Surface immunoglobulin receptors of rabbit lymphoid cells. Evaluation of fluorescent staining with antibodies to immunoglobulin light chain allotypes.

Rabbit lymphoid cells were stained with fluorescein-labelled antiallotype antibodies. The double layer technique was found to be more sensitive than the direct staining. Rabbit B cells are stained only via their surface immunoglobulin (sIg) receptors and not via the receptors for the Fc portion of the IgG. Peritoneal exudate macrophages do not carry sIg receptors and are stained via their Fc receptors. Removal of protein aggregates from the system and use of reagents prepared from F(ab')2 immunoglobulin fragments prevent staining of the macrophages through their Fc receptors. There was a good agreement between the percent of RABELA-positive and sIg-containing spleen cells. In appendix there were approximately 20% more RABELA-positive than sIg-positive cells.

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Basilea rabbit immunoglobulins: detection and characterization by specific alloantiserum.

Evidence is provided for the existence of the Fbbas (Basilea) gene product (allotype). Specific antisera were raised by immunization of rabbits that did not possess the Basilea genes. With the help of these antisera, the Basilea allotype was detected in sera from rabbits, homozygous and heterozygous with respect to Basilea gene. The Basilea gene is expressed on a very low proportion of immunoglobulin molecules. The isoelectric point of the Basilea light chains is distinct from that of the lambda-light chains (peaks at pH 4.7 and 5.5, respectively). Sera from a large proportion of Ab9-positive rabbits of the Basel Institute for Immunology that were heterozygous at the Ab locus reacted with the anti-Basilea serum, even though they could no possess the Basilea gene at the Ab locus. Sera from Ab9-positive rabbits from Toronto were Basilea-negative. It was suggested that Ab9 and Basilea allotypes are controlled at closely linked loci. Ab9 haplotype prevalent in the Basel animal colony, possesses both Ab9 and Basilea genes, whereas the corresponding Toronto haplotype has only the Ab9, but not Basilea gene. The formation of the Basilea genotype was attributed to a crossing over, during which the Ab9 and Basilea genes separated.

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Age-dependent changes in tolerizability with rabbit gamma-globulin in the Biozzi high and low-responder lines of mice.

The antibody response to rabbit gamma-globulin (RGG) of high-responder, but not of low-responder Biozzi mice decreased with age. Injection with aggregate-freed RGG reduced the response of high-responder but not of low-responder mice to subsequent injections with aggregated RGG. This reduction in the antibody response, formed by high-responder mice, decreased with increasing age; aggregate-freed RGG appeared to sensitize 6-month-old low-responder mice to a subsequent injection with aggregated RGG. When animals, not pretreated with aggregate-freed RGG, were immunized with RGG and lipopolysaccharide (LPS), the immune response was greatly enhanced. The response of both pretreated low and high responders was substantially smaller than that of corresponding animals which were not given aggregate-freed RGG, prior to immunization. LPS revealed an inhibitory effect on low-responder mice of aggregate-freed RGG, which was not detected upon immunization with heat-aggregated RGG alone. The involvement of nonspecific suppressor cells and of B cell tolerance in low-responder mice is discussed.

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