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B Cinader

Publications and source records attributed to B Cinader.

At least 19 recordsLinked to original sources

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.

Aging

Purification of rabbit B spleen cells by removal of adherent and of T cells.

B lymphocytes from the rabbit spleen were freed of T cells by removal of cells which formed rosettes with papain-treated rabbit erythrocytes. Additional purification could be achieved if fractionation by rosette removal was preceded by removal with a magnet of cells which adhered to or ingested poly L-lysine coated iron core particles. Cell yield and purification were assessed by complement mediated cytotoxic kill of B and T cells with antibody directed against RABELA and RTLA, respectively. Other criteria depended on determination of the number of Fc receptor bearing cells and of thymidine uptake by cells which were stimulated with concanavalin A, PHA or with antibody directed against the allotypic specificity of receptor Ig light chains. Purified preparations of B cells were obtained in a yield of about 20% of the B cells in the original spleen and contained less than 10% of cells which were not B cells. This method allows purification which does not interfere with the membrane of the isolated cells.

Animals

Regulatory influences on the response of rabbit T cells to concanavalin A and phytohaemagglutinin.

The proliferative response, induced in rabbit spleen cells by concanavalin A (Con A) and phytohaemagglutinin (PHA), is abolished when T cells are killed with antibody against rabbit thymus lymphocyte antigen (RTLA) in the presence of complement. The response was examined with purified spleen T cells, to which various helper cell fractions were added; it could be shown that B cells help the responding T cells. The helper effect in the response to PHA is abolished and the response to Con A is reduced by any manoeuvre which destroys or removes B cells. Help by B cells is given when helper cells have lost proliferative capacity as a consequence of mitomycin-C treatment. Spleen cells adhering to the walls of culture tubes help suspended T spleen cells in their response to Con A. This help could be abolished by complement mediated cell kill with antibody to rabbit bursal equivalent lymphocyte antigen (RABELA). On the other hand, the helper effect in Con A response was increased when T cells were removed. Thus the response of T cells to Con A is regulated by helper B cells and suppressor T cells.

Animals

A suppressor cell in the response of rabbit T cells to Con A.

The response to Concanavalin A is regulated by a helper cell, described elsewhere (4), and by a suppressor cell, described in this paper. This suppressor cell is an adherent T cell with Fc receptors. Evidence for properties of the suppressor cell was obtained by two types of experiments: 1) regulatory cells gave more help if Fc-bearing subpopulations were removed from them, i.e. the suppressor cell could not be removed with Degalan beads, coated with anti-allotype antibody, but not with beads, coated with F(ab')2 fragments of the antibody; 2) help for T cells, in their response to Con A, was augmented when T cells were eliminated from the regulating adherent cell preparation. Thus, the response of spleen T cells to Con A is regulated by two adherent cells, a B helper cell and a T suppressor cell. We have previously shown that the response to phytohemagglutinin (PHA) is regulated by an adherent helper cell (4). We have found no evidence, in the present study for an adherent suppressor cell which participates in the T cell response to PHA.

Animals

Immunoglobulin synthesis by thymus B cells.

Rabbit lymphoid cells transferred to newborn recipients synthesized donor-type immunoglobulin. Elimination of donor T cells did not affect this synthesis of donor immunoglobulin, while elimination of B cells abolished or significantly decreased the synthesis. The synthetic capacity of B cells from thymus was thirty-four times greater than the synthetic capacities of B cells from spleen, fifty-five times greater than that of mesenteric lymph nodes and 180 times greater than that of appendix cells. Synthetic activity of spleen cells ceased before the tenth day after transfer, while thymus cells might continue to synthesize immunoglobulin for a longer time. This was shown by comparing half-lives of donor immunoglobulin in the recipients' sera. Increasing the number of injected spleen cells (from 2 x 10(6) to 120 x 10(6)), resulted in a corresponding increase in donor Ig synthesis. With thymus cells, donor immunoglobulin increased with cell numbers up to 2 x 10(7) cells, above this dose there was no further donor immunoglobulin increase in the recipients' serum.

Animals

Rabbit B spleen lymphocytes and T helper cells. I. Responsiveness to mitogens of B cell subpopulations of different sedimentation velocities and subpopulations bearing or lacking Fcgamma receptors.

The response to anti-allotype (anti-Ab4), Nocardia Water Soluble Mitogen (NWSM), pneumococcal polysaccharide type III (SSS III), and human Fc fragments of various purified and unfractionated rabbit spleen cell populations was determined in terms of 3H-thymidine up-take. B cells were isolated either from untreated suspensions of spleen cells or from suspensions from which adherent and phagocytic cells were removed. The purification factor was greater than the enhancement of 3H-thymidine uptake by anti-Ab4, NWSM, and SSS III as compared with the response of unfractionated spleen cells. It thus appears that a helper cell was involved: the mitogen response of purified B cells was enhanced by the addition of T cells. B subpopulations were separated by sedimentation or by rosetting, which allowed us to separate Fcgamma receptor-bearing cells from cells that did not possess this receptor. There were differences between cells responding to B mitogens not only in sedimentation velocity but also in the absolute number of cells. B cells bearing the Fcgamma receptor were less responsive to anti-Ab4 and more responsive to SSS III, NWSM, and human Fc than were B cells lacking the Fcgamma receptor.

Animals

Effect of cyclic nucleotides, isoproterenol and cholera toxin on DNA synthesis triggered by mitogens.

The effect of cyclic nucleotides, isoproterenol and cholera toxin on phytohaemagglutinin (PHA), concanavalin A (Con A) and anti-allotype-induced rabbit lymphoid cell proliferation was examined. Cholera toxin in concentrations ranging from 10(-8) microgram to 1 microgram per culture inhibited DNA synthesis, triggered by PHA, Con A and nocardia water-soluble mitogen (NWSM). It had the opposite effect on stimulation with antibodies directed against allotypic specificities of the immunoglobulin light chains: over the entire range of tested concentrations, cholera toxin stimulated DNA synthesis triggered by antibodies to Ab4, Ab5, Ab9 and to Aa1 allotypic specificities. Relatively high concentrations of dibutyryl adenosine 3':5'-cyclic monophosphate (cAMP) and isoproterenol (10(-3) M) inhibited mitogen-stimulated thymidine incorporation; lower concentrations (10(-9) M) had an enhancing effect. A similar enhancing effect was observed when high (10(-3) M) concentrations of dibutyryl guanosine 3':5'-cyclic monophosphate (cGMP) were used.

Animals

Temperature stress and immunity in mice: effects of environmental temperature on the antibody response to human immunoglobulin of mice, differing in age and strain.

Physiological responses at different ambient temperatures and temperature-dependent changes in immune responsiveness are polymorphic. At 4 degrees C, the antigen elimination from the bodies of SJL and C57Bl/6 mice is accelerated. In SJL, but not in C57Bl/mice, the half-life of antigen elimination decreased between the ages of 3 and 11 weeks. Parental mice and their F1 hybrids showed a fall in rectal temperature, which was greatest in young animals. Hypothermia was greater in C57Bl/6 than in SJL and F1 hybrids; in 3 week old C57Bl/6 it resulted in high mortality. The response to aggregated human immunoglobulin (HGG) was evaluated by (a) the number of animals with detectable antibody, (b) the minimal dose of antigen eliciting detectable antibody, and (c) the mean titre of haemagglutinating antibody. SJL mice were more responsive than C57Bl/6 mice. Low antibody formation in the secondary response was dominant, i.e. the amount of antibody produced by (SJL X C57Bl/6)F1 mice was the same as that produced by the parental C57Bl/6 strain. In a primary response, the quantity of antibody varied with the age of the immunized animal; 18 week old mice responded to lower minimal doses of antigen and produced more haemagglutinating antibody than 3 week old animals. After a second injection with HGG, SJL but not C57Bl/6 mice produced more antibody when kept at 14 degrees C rather than at 22 degrees C or 30 degrees C, and produced the lowest antibody titres when kept at 4 degrees C. The relation between ambient temperature and the response of the SJL mice was dominant over that of the C57Bl/6strain. Primary differed from secondary responsiveness in that neither strain produced significantly lower titres when ambient temperature fell to 4 degrees C; only 18 week old SJL mice responded with a marginal decrease in peak antibody production. The described polymorphism may affect both the individual capacity to cope with low temperatures and the evolutionary adaptation of a species to climatic extremes.

Age Factors

Purification of rabbit T-derived (Ig-) lymphocytes.

Rabbit peripheral blood cells were rosetted by means of mixed agglutination technique described by Coombs et al. and the unrosetted Ig-, T-derived lymphocytes were separated in Ficoll-Triosil gradient. The cells which did not rosette in mixed agglutination reaction represented highly purified T-derived (Ig-) lymphocytes, as evidence by their response to T and B rabbit cell mitogens, their cytotoxic reactivity versus rabbit thymus lymphocyte antiserum (RTLA), and by failure to be stained with labelled anti-rabbit immunoglobulins antibodies and antibodies against allotypic specificities of the a and b series.

Animals

Resistance to tolerance induction and age-dependent cellular changes in SJL mice.

SJL mice became resistant to tolerance induction between the 2nd and 6th week of life. The effect on tolerance induction of radioresistant accessory (A) cells does not depend on the age of the donor, i.e. is the same whether the A-cell donor is 3 or 12 weeks old. In the thymectomized recipient, reconstituted with spleen cells of 12-week-old donors, resistance to tolerance is greater than in the corresponding intact animal. Resistance to tolerance is due to a change in the T cells, occurs at a different rate in the T cells of thymus and spleen, and my be due to change in the relative proportion of different T-cell subpopulations.

Aging

Tolerance induction as an index of age-related changes.

Tolerance to rabbit gamma globulin RGG) can be induced in newborn or three week old mice of all strains tested. In six week old SJL or NZB mice there is marked resistance against tolerance induction to RGG. This resistance increases with increasing age and is completed by the age of 12 weeks. Resistance to tolerance can be observed in 3 week old SJL animals when human IgG3 but not when human IgG1 or RGG is employed as tolerogen. Using IgG3, resistance to tolerance induction can be demonstrated in 28-34 week old A/J, C57BL/6J and DBA1/J mice. Thus resistance to tolerance induction seems to be a concomitant of aging; SJL and NZB differ from other strains only by the age at which this change is apparent. By the 6th week of age, SJL and NZB mice develop marked resistance to tolerance induction with RGG, and so do hybrids between these two strains; there is no complementation with respect to resistance against tolerance induction. Aggregate-freed iodinated rabbit gamma globulin (125I-RGG) but not mouse immunoglobulin is eliminated much more rapidly from the body of normal 6 week old SJL and NZB mice than from the body of hybrids. Complementation in the hybrids might occur and prevent a response to small quantities of aggregate-freed RGG.

Aging

Rabbit lymphoid cells. I. T-cell mitogens, cell volume and adherence properties as probes for cellular heterogeneity.

Thymus-derived cell populations were characterized by sedimentation velocity in the Earth's gravitational field, by adherence properties, and in terms of the thymus-specific antigen RTLA. T cells, responding to mitogens, could be shown to be a subpopulation of RTLA-bearing cells and to have a relatively large volume. The size distribution of mitogen-responsive cells from different individuals showed some variation, but in general large spleen cells took up less thymidine per 10(6) cells than did large cells from other lymphoid organs. Upon stimulation with concanavalin A (con A) small popliteal lymph node cells took up more thymidine per 10(6) cells than did small thymus cells. The corresponding small cells of mesenteric lymph node and spleen took up intermediate quantities of thymidine. Thymus-derived cells that were resistant to complement-mediated cell kill with RTLA antiserum showed greater responsiveness to con A than did the original cell preparations. Non-adherent cells incorporated more thymidine when stimulated with phytohaemagglutinin (PHA) than when they were stimulated with con A. Lightly adherent cells were relatively more responsive to con A stimulation and firmly adherent cells were less responsive to both. The findings were discussed in terms of the density of RTLA on the membranes of T cells. In adherence and in sedimentation velocity fractionation, the relative yield of nucleated cells always exceeded the yield of PHA- and con A-responsive cells. The differential separation of mitogen responsive and of co-operating cells were considered as a possible cause of this deficit.

Animals

Rabbit lymphoid cells. II. Anti-allotype antisera, lipopolysaccharide and other bacterial and fungal mitogens as probes for the identification of B-cell subpopulations.

Removal of adherent cells or complement-mediated killing of rabbit thymus lymphocyte antigen (BTLA) bearing rabbit T lymphocytes did not abolish the responsiveness (increased thymidine incorporation) of lymphoid cells to antibody against immunoglobulin allotype, Nocardia water-soluble mitogen (NWSM), pneumococcal polysaccharide SIII (PPSIII), S. abortus lipopolysaccharide (LPS), lipid A conjugated to bovine serum albumin and a crude preparation containing C polysaccharide from the cell wall of Diplococcus pneumoniae. Isologous and heterologous antisera, directed against different portions of the Ig receptor, differed in their capacity to enhance thymidine incorporation. The difference in mitogenicity of these antisera was discussed in terms of the accessibility of cell-bound immunoglobulin receptor sites. Spleen cells, responsive to anti-allotype (Ab4) antiserum and B-cell mitogens, NWSM and PPSIII, were characterized by velocity sedimentation. The mean volume of NWSM- and PPSIII-responsive cells was larger than that of the cells responsive to anti-allotype antiserum. Fractionation of spleen cells on glass bead columns yielded a population of non-adherent cells which were two to six times as responsive to anti-Ab4 antiserum as the original spleen cell suspension. The responsiveness of peripheral blood lymphocytes to anti-Ab4 antiserum was significantly greater than that of spleen cells. On the other hand, spleen cells were more responsive to PPSIII than were cells from the peripheral blood, the popliteal and the mesenteric lymph nodes.

Animals

Tumor colony formation by Friend virus-infected cells in immunosuppressed mice.

We have investigated the role of host immunological factors in the formation of "tumor colonies" in the spleens of unirradiated C57BL/6 X C3Hf/Bi FI mice 9 days after i.v. injection of spleen cells from Friend virus (FV)-infected C3Hf/Bi donors. Pretreatment of hosts with antilymphocyte serum (ATS) increased the number of tumor colonies. Pretreatment with formalinized FV-infected cells had the opposite effect, and ATS diminished the inhibitory effect of preimmunization. Cell suspensions from 11 individual FV-infected donors were examined. The suspensions differed with respect to their behavior on transplantation into untreated and ATS-pretreated F1 hybrid hosts. With several suspensions, the number of tumor colonies produced was approximately proportional to the number of cells injected; in all of these, ATS increased the slope of the line relating colony number to cell number. With most of the suspensions, tumor colony-forming efficiencies in untreated hosts strikingly decreased with increasing number of cells injected; ATS induced an increase in the number of tumor colonies and rendered the colony-forming response more nearly proportional to cell number. With two suspensions, few or no colonies developed; pretreatment with ATS had no significant effect. When the 11 cell suspensions were considered together, a proportional relation was found between the magnitude of the ATS effect (i.e., colony number in the presence of ATS minus colony number in the absence of ATS) and the colony-forming efficiency in ATS-treated mice. The ATS effect on the average was equivalent to a 2-fold increase in tumor colony-forming efficiency. We interpret these findings to indicate that two factors interact to determine the number of tumor colonies produced by spleen cells from FV-infected C3H donors in untreated F1 hybrid hosts. One is a property of the FV-infected cell population and includes its frequency of tumor colony-forming units; this factor varies widely among different cell suspensions. The other is a property of the tumor colony-forming units-host interrelationship and includes the vulnerability of tumor colony-forming units to the host immune response elicited by the injected cells; this factor appears to be constant with different cell suspensions. The present results show that the two factors can be dissociated in immunosuppressed hosts.

Animals