Search PubMed⌕ Search

Biomedical subjects

R Asofsky

Publications and source records attributed to R Asofsky.

At least 109 records · Page 6Linked to original sources
PubMed1972

Genetic factors controlling anti-sheep erythrocyte antibody response and immunoglobulin synthesis in backcross and F2 progeny of mice genetically selected for "high" or "low" antibody synthesis.

Agglutinin responses to sheep erythrocytes and immunoglobulin heavy chain phenotypes determined in F(1), F(2), and backcross progeny of mice genetically selected for high and low antibody synthesis indicated that an immune response gene for sheep erythrocytes is linked to the immunoglobulin heavy chain allotype. Mice homozygous for the phenotype of the high line had significantly higher titers than mice homozygous for the phenotype of the low line. An association was also observed in some progeny of the backcross of the F(1) generation with the low line. However, the control of the immune response was clearly multigenic since heterozygous mice of the same phenotype (2/3, 5) resulting from the two backcrosses (high and low) had very different immune responses. Immunoglobulin levels in the same progeny showed no linkage to the immunoglobulin allotype but a rather simple pattern of inheritance.

Animals↗
PubMed1972

Synergy among lymphoid cells mediating the graft-versus-host response. IV. Synergy in the GVH reaction quantitated by a mortality assay in sublethally irradiated recipients.

A mortality assay was used to quantitate graft-versus-host (GVH) reactions in sublethally irradiated (400 R) neonatal (C57BL/6 x BALB/c)F(1) recipients of BALB/c lymphoid cells from various tissues. The probit of the 35 day cumulative per cent of mortality was a linear function of the logarithm of the cell inoculum for any tissue; reactivities of different tissues fell on a series of parallel lines. Peripheral blood leukocytes (PBL), the most active cells, were about 30 times as active as thymocytes, the least active cells studied; femoral lymph node cells and spleen cells were about 23 and 8 times as reactive as thymocytes, respectively. The average survival time of recipients of thymocytes who eventually died was nearly a week longer than that of recipients of comparably lethal numbers of PBL, lymph node, or spleen cells. Mixtures of PBL and thymocytes gave levels of 35 day mortality significantly greater than those expected if the reactivities of the mixture had been merely the sum of the reactivities of the components measured separately, thereby confirming in any assay independent of host splenomegaly the synergistic interaction of thymocytes and PBL in the GVH reaction. Both populations of cells in the mixture had to be allogeneic to the host in order to observe this synergy. The kinetics of cumulative mortality observed for mixtures of PBL and thymocytes were indistinguishable from those seen with thymocytes alone, indicating activation of the latter cell type. Finally, comparison of the relative abilities of different cell populations to cause splenomegaly on the one hand and lethal runting on the other has raised the possibility that expression of different effector functions of cell-mediated immune reactions may in fact be initiated by distinct cells.

Animals↗
PubMed1972

Synergy among lymphoid cells mediating the graft-versus-host response. 3. Evidence for interaction between two types of thymus-derived cells.

Two types of thymus-derived (T) lymphocytes have been shown to cooperate in the induction of graft-versus-host responses. One cell type is found in highest concentrations in the peripheral blood and lymph node, is extremely sensitive to anti-thymocyte serum (ATS) in vivo, and is probably part of the recirculating lymphoid cell pool (3). The second cell type, found in highest concentrations in the thymus and spleen, is relatively resistant to small doses of ATS in vivo. Both cell types are substantially depleted after neonatal thymectomy. Moreover, since synergism was also obtained using appropriate mixtures of cells from either parental strain in F(1) hosts, it was possible to show that the nonrecirculating cells determined the specificity of the response and were probably the precursors of effector cells in this response. The recirculating T cell appeared to amplify this response. The implications of these data are discussed.

Animals↗
PubMed1972

Immune responses in vitro. IV. Suppression of primary M, G, and A plaque-forming cell responses in mouse spleen cell cultures by class-specific antibody to mouse immunoglobulins.

The suppressive effects of monospecific goat anti-mouse globulins on primary immunoglobulin class-specific plaque-forming cell responses in mouse spleen cell cultures were investigated. Anti-micro suppressed responses in all immunoglobulin classes, whereas anti-gamma(1) and anti-gamma(2) suppressed the gamma(1) and gamma(2) responses but not gammaM or gammaA responses, and anti-gammaA suppressed only gammaA responses. The mechanism of action of the anti-micro was studied in detail because of its suppression of responses in all immunoglobulin classes. The anti-micro was specific for micro-chain determinants; its activity was dose dependent, but was not mediated by killing cells with surface micro-chain determinants. Free gammaM but not gammaG myeloma proteins in solution effectively competed with micro-bearing cells for the anti-micro. An excess of anti-micro was necessary in the cultures for 48 hr to insure complete suppression of 5-day responses. However, after removal of excess anti-micro at 48 hr, responses could be stimulated by newly added antigen in cultures where incubation was prolonged to 7 days. Anti-micro was most effective when added at the initiation of cultures and had no suppressive effect when added at 48 hr. Excess antigen did not effectively compete with anti-micro for antigen receptors. Precursors of antibody-forming cells were shown to be the cell population where the suppressive activity of anti-micro was mediated. The experiments suggest that anti-micro combines with micro-chain determinants in antigen-specific receptors on the surfaces of antibody-forming cell precursors, prevents effective stimulation by antigen and subsequent antibody production. To explain suppression of responses in all Ig classes by anti-micro, several models were proposed. It is not possible to determine from the data whether stimulation of precursor cells with gammaG or gammaA receptors requires concommitant stimulation of separate cells with only gammaM receptors, or whether cells bearing gammaM receptors are precommitted to or differentiate into cells capable of synthesis of other Ig classes, or whether receptors of gammaM and another Ig class are present on some virgin precursors or the second Ig receptor appears after antigenic stimulation.

Animals↗
PubMed1972

Immune responses in vitro. V. Suppression of M, G, and A plaque-forming cell responses in cultures of primed mouse spleen cells by class-specific antibody to mouse immunoglobulins.

Suppression of Ig class-specific PFC responses by class-specific antibody to mouse immunoglobulin was studied in cultures of spleen cells from immunized mice. In contrast to cultures from normal mice where anti-micro suppressed responses in all Ig classes, anti-micro had progressively less suppressive effect on gamma(1) and gamma(2) responses in cultures from immunized mice with time after immunization. This was most pronounced at 10 days after immunization when anti-micro suppressed gammaM and gammaA responses, but had no or slight effect on gamma(1) or gamma(2) responses which were still suppressed with anti-gamma(1) and anti-gamma(2). These changes in precursor cell susceptibility to anti-micro were antigen specific.

Animals↗
PubMed1972

Suppression of immunoglobulin class synthesis in mice. I. Effects of treatment with antibody to -chain.

Germfree BALB/c mice have been treated from birth with intraperitoneal injections of purified goat antibodies to mouse IgM. The treated mice, and controls which had received an equivalent amount of goat gamma-globulin, were sacrificed at 8 or 13 wk of age. Compared to controls, mice given anti-micro (a) had very few germinal centers in spleen and lymph node, (b) had decreased numbers of mature plasma cells synthesizing IgM and IgG1 in spleen, and virtual absence of IgA-synthesizing plasma cells in the gut, (c) had greatly diminished numbers of B lymphocytes bearing membrane-bound immunoglobulins of the IgM, IgG1, IgG2, and IgA classes in spleen, (d) had reduced synthesis of IgM, IgG2, and IgA by in vitro spleen cultures, and (e) had significant decreases in serum levels of IgM, IgG1, IgG2, and IgA. The treated animals failed to make antibodies to ferritin after hyperimmunization, and lacked natural antibodies to sheep erythrocytes. These results indicate that cells ultimately committed to synthesis of IgG1, IgG2, and IgA immunoglobulins are derived from cells which have expressed IgM determinants at an earlier stage of differentiation. They are consistent with a proposed two-stage model for plasma cell differentiation. The first stage is antigen independent, involves sequential activation of Cmicro, Cgamma, and Calpha genes by progeny of a single stem cell, and results in the formation of B lymphocytes bearing membrane-bound recognition antibodies of each class. The second, antigen-dependent, stage results in formation of mature plasmacytes and memory cells.

Animals↗
PubMed1971

Immune responses in vitro. 3. Development of primary gamma-M, gamma-G, and gamma-A plaque-forming cell responses in mouse spleen cell cultures stimulated with heterologous erythrocytes.

We have demonstrated for the first time that mouse spleen cells stimulated in vitro with heterologous erythrocytes developed immunoglobulin class-specific gammaM, gamma(1), gamma(2a+2b), and gammaA plaque-forming cell (PFC) responses. A modification of the hemolytic plaque technique, the addition of goat anti-mouse micro-chain antibody to the assay preparation, specifically prevented development of all gammaM PFC and enabled accurate and reproducible enumeration of immunoglobulin class-specific PFC after treatment with appropriate monospecific anti-globulins and complement. Culture conditions, with regard to medium, atmosphere, agitation, and spleen cell densities, were similar to those previously shown to support only gammaM PFC responses. Evaluation of the kinetics of appearance of PFC showed that gammaM PFC reached maximum numbers on days 4-5; the magnitude of this response was 3-10 times greater than gamma(1) gamma(2a+2b), or gammaA PFC which reached maximum numbers on days 5-6. Optimal erythrocyte antigen dose for gammaM PFC responses was 10(7)/culture, whereas a dose of 10(6) erythrocytes/culture consistently stimulated optimal gamma(1) gamma(2a+2b), or gammaA PFC responses. Investigations of the effects of anti-erythrocyte antibody on gammaM and gammaG PFC responses indicated that antibody suppressed these responses by neutralizing the effective antigenic stimulus at the macrophage-dependent phase of the response. At the same antibody concentration, gammaG PFC responses were more effectively suppressed than gammaM PFC responses. Further, gammaG responses could be almost completely suppressed by antibody as long as 48 hr after initiation of cultures, whereas gammaM PFC responses could only be completely suppressed during the first 24 hr. These results were discusssed in terms of the role of antigen in the stimulation gammaM and gammaG antibody.

Animals↗
PubMed1970

Serum concentrations and allotypes of immunoglobulins in two lines of mice genetically selected for "high" or "low" antibody synthesis.

Random-bred Swiss mice were selectively bred for 16 generations; selection was based on their agglutinin response to sheep and pigeon erythrocytes to produce a high and a low responder line. The serum levels of individual immunoglobulins differed significantly in these two lines before immunization. The differences in the levels of immunoglobulins were much more marked after immunization with pigeon or sheep erythrocytes. Greater differences between the two lines were noted in IgM and IgG levels than in IgA. Another remarkable finding was the presence of different immunoglobulin phenotypes in the two lines. The high responders were homozygous or heterozygous for heavy-chain linkage groups found separately in the prototype BALB/c and C57BL inbred strains. The low responders were homozygous for a heavy-chain linkage group not present in bred mice in the United States, but observed as a recombinant type among wild mice probably representing a crossover between the heavy-chain linkage groups of the prototype DBA/2 and NH inbred mice.

Animals↗
PubMed1970

Synergy among lymphoid cells mediating the graft-versus-host response. I. Synergy in graft-versus-host reactions produced by cells from NZB-Bl mice.

The ability of spleen cells from young (3 month) and old (1 yr) NZB mice to induce GVH reactions in newborn C57BL/6N mice was compared quantitatively using the Simonsen spleen assay. Young NZB cells were five times more reactive than cells from older mice. The minimum number of cells producing detectable reactions was 2 x 10(6) for the young and 10 x 10(6) for the old. Young and old cells combined and injected together produced GVH reactions quantitatively similar to those obtained with inocula composed of young cells alone. Mixtures of two cell populations producing no detectable reactions when injected separately into different recipients (1 x 10(6) young cells and 4 x 10(6) old cells) produced reactions approximately equal to those obtained with 5 x 10(6) young cells. As few as 0.25 x 10(6) young cells were sufficient to effect a reaction when combined with 4.75 x 10(6) old unreactive cells. Viability of both cell populations was essential for GVH reactivity. This evidence of synergy in GVH reactions indicates that old NZB spleen cells can be rendered immunologically more reactive in the presence of a normally reactive population.

Age Factors↗
PubMed1970

Synergy among lymphoid cells mediating the graft-versus-host response. II. Synergy in graft-versus-host reactions produced by Balb-c lymphoid cells of differing anatomic origin.

The capacity of cells from different lymphoid tissues obtained from Balb/c mice to produce graft-vs.-host (GVH) reactions was quantitatively determined in C57BL/6N by Balb/c F(1) hybrid recipients. Synergistic responses were observed when small numbers of cells from lymphoid tissues that were rich in GVH activity such as spleen and femoral lymph node were combined with weakly reactive thymus cells. Thymus and spleen cells obtained from 1-wk old mice were separately inactive but produced moderate GVH reactions when combined in equal proportions. GVH activity of spleen cells from mice thymectomized at 3 days of age was partially restored by the addition of small numbers of spleen or thymus cells from adult mice. Changes in ratio between the two cell populations markedly affected the degree of synergy. Synergy was not observed when Balb/c cells were combined with Balb/c x C57BL/6N F(1) hybrid cells and inoculated into C57BL/6N recipients, but was demonstrated when Balb/c and C57BL/6N cells were combined and inoculated into F(1) recipients, indicating that a genetic disposition to mount GVH reactions in both populations is required to produce synergy. The data indicate that at least two cell types are necessary for GVH reactions, and that synergy between cell populations results from favorable adjustments in the ratio between these two cell types.

Animals↗
PubMed1970

Immunoglobulin synthesis by salivary gland lymphoid cells in Sjögren's syndrome.

The synthesis of immunoglobulins by cells infiltrating the labial salivary glands has been studied by radioimmunoelectrophoresis in 20 patients with Sjögren's syndrome (SS) and in 14 control patients with related disorders. The patients with SS were producing significantly greater quantities of IgG, IgM, and IgA. Synthesis of IgG and IgM correlated with the degree of lymphoid infiltration but not with serum immunoglobulin concentration. Patients with SS and rheumatoid arthritis (RA) showed greater synthesis of IgG and IgM than those with uncomplicated RA. The only extensive lymphoid infiltration was seen in patients with SS. One patient with SS and primary macroglobulinemia was synthesizing the paraprotein in the lip biopsy as well as in the bone marrow. These results establish the immunologic competence of the infiltrating lymphoid cells and suggest their origin from an extrasalivary source.

Adult↗