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M A Aldo-Benson

Publications and source records attributed to M A Aldo-Benson.

At least 19 recordsLinked to original sources
PubMed1986

An in vitro model for clonal anergy in continuously growing antigen-specific B-cell lines.

Two continuously growing nonmalignant B-cell lines specific for the hapten DNP have been used to study tolerance in developing B cells. These cell lines have previously been shown to consist of small cells without sIgM but with cytoplasmic mu chains, and mature sIgM- and sIgD-bearing cells. When the sIgM-negative cells are placed in culture, mature DNP-specific B cells begin to appear. The studies reported here have shown that when these cell lines were propagated in the presence of either 200 micrograms/ml or 1 mg/ml of the tolerogen DNP-MGG there was no inhibition of cell line growth as measured by thymidine incorporation, and no inhibition of receptor expression by maturing B cells. The cell line lymphocytes propagated in the presence of 200 micrograms/ml DNP-MGG for 7, 30, 45, or 60 days became tolerant and the tolerance persisted for at least 6 days after removal of DNP-MGG. However, tolerance was lost between 6 and 10 days after removal of DNP-MGG. Propagation of the cell lines for 30 days in either DNP-KLH or DNP-Ficoll produced the same results. Limiting dilution cultures of cell line lymphocytes made tolerant by growing them for 30 days in the presence of DNP-MGG demonstrated that there was a marked decrease in precursor frequency compared to controls. However, cell line lymphocytes made tolerant by a 48-hr incubation with DNP-MGG did not have a significant decrease in precursor frequency. These data suggest that tolerance induced by growing these cell lines in the presence of DNP-MGG is a valid in vitro model of tolerance in developing antigen-specific B cells. Tolerance induced in this model is consistent with the clonal anergy hypothesis, but requires the continued presence of DNP-MGG to maintain unresponsiveness. This suggests that clonal anergy can occur in B cells but may not be the sole mechanism of self tolerance for those antigens which are sequestered from the immune system.

Animals↗
PubMed1985

Macrophage-derived soluble factors mediate suppression induced by 2,4-dinitrophenyl-conjugated mouse IgG in hybridoma cells.

Our laboratory has established that 2,4-dinitrophenyl-conjugated mouse IgG (DNP-MGG) can specifically suppress proliferation, antibody synthesis, and secretion in vivo in two anti-DNP secreting cell lines: hybridoma 35-12 and myeloma MOPC-315. In the present study an in vitro system was used to further analyze the mechanism of suppression of hybridoma 35-12 cells (HC) by DNP-MGG. It was found that DNP-MGG-induced suppression of HC requires macrophages (M phi) and occurs only in eclipsed HC which are mainly small, nonsecreting cells. The M phi-mediated suppression is DNP specific, requires no M phi-HC cell contact, and does not involve killing of eclipsed HC. M phi culture supernatant alone cannot mediate suppression, but supernatants obtained by culturing M phi with either HC or supernatant from HC culture can mediate suppression of eclipsed HC in the presence of DNP-MGG. DNP-MGG is not required for the generation of effective M phi factors, but it is required for suppression of HC in the presence of M phi factors. Indomethacin cannot reverse M phi-mediated suppression, suggesting prostaglandins may not be the M phi factors. These data suggest that M phi-derived factors which are not prostaglandins in nature may play a role in B-cell regulation and in B-cell suppression induced by tolerogenic forms of antigen.

Animals↗
PubMed1985

Tolerance and immunity in antigen-specific B-lymphocyte lines: early receptor binding of either antigen or tolerogen initiates an immune response.

Studies of the effect of tolerance-inducing compounds on B lymphocytes have been complicated by the fact that it is technically difficult to completely isolate the antigen-specific B cell from the effects of T cells or T-cell factors. We have used our cell lines of nonmalignant dinitrophenyl (DNP)-specific B lymphocytes derived from normal mice, which have no contaminating T cells, to study the effect of DNP-murine IgG2a (DNP-MGG), a tolerogen which is not normally immunogenic, on antigen-specific B lymphocytes. Preincubation with DNP-MGG for 48 hr, both in the presence and absence of T-cell factors from EL-4 supernatant prior to adding the antigen DNP-Ficoll, can induce tolerance in cell line B lymphocytes. The suppression is antigen-specific since preincubation with fluorescein-MGG or unconjugated MGG does not suppress the anti-DNP response. At least a 36-hr incubation is required for tolerance induction in B lymphocytes, but a 6-hr preincubation with DNP-MGG augments the immune response to DNP-Ficoll. Lymphocytes incubated for 6 or 24 hr with DNP-MGG prior to adding EL-4 supernatant and filler cells without DNP-Ficoll exhibited an immune response equal to that elicited by DNP-Ficoll and T-cell factors. A 6-hr pulse with a DNP-conjugated polymer of D-glutamic acid and D-lysine (DNP-dGL), a B-cell tolerogen which does not bind to Fc receptors, elicited the same immune response as seen with a 6-hr pulse of DNP-MGG but a 48-hr preincubation with DNP-dGL induced tolerance. Thus, it is likely that the initial binding of the tolerogen to the immunoglobulin receptor on the mature B cell elicits an activation signal similar to that seen with the antigen. The suppressive effect of the tolerogen itself appears to occur at a later stage of the process of the B-cell activation, proliferation, and differentiation.

Animals↗
PubMed1984

Central suppression of monoclonal B cells: DNP-MGG suppresses proliferation and immunoglobulin synthesis in anti-DNP-secreting hybridoma and myeloma.

Our laboratory has established that 2,4-dinitrophenyl-conjugated mouse IgG (DNP-MGG) can specifically suppress the anti-DNP secretion in hybridoma 35-12 and plasmacytoma MOPC-315 cells. To further study the mechanism of this suppression, the effect of DNP-MGG on anti-DNP synthesis and cell proliferation was investigated in these cell lines. Cultured tumor cells (1 X 10(6] were injected ip into syngeneic mice. These mice were then given either 1 mg MGG or 1 mg DNP-MGG. At different days after injection, tumor cells obtained from these mice were assayed for anti-DNP secretion, anti-DNP synthesis, cell proliferation, and tumor cell size. When the anti-DNP secretion was suppressed by DNP-MGG, the intracellular synthesis of anti-DNP, demonstrated by [3H]leucine incorporation into DNP-binding activity, was also suppressed. Simultaneous assays of [3H]thymidine incorporation demonstrated that proliferation was also suppressed. Tumor cells injected ip into mice normally become small nonsecreting cells and later return to preinjection size and secrete antibody. Those cells whose antibody synthesis and proliferation were suppressed by DNP-MGG remained smaller.

Animals↗
PubMed1983

Specific suppression of hybridoma immunoglobulin secretion by hapten-conjugated mouse IgG: a model of B-cell tolerance.

In an effort to establish a model system for studying B-cell tolerance, the effects of hapten-conjugated isologous mouse IgG on the secretion of antibody by a mouse hybridoma cell line were studied. The hybridoma cell line 35-12 (HC) secretes IgM antibody to the hapten dinitrophenyl (DNP). After HC cells are injected intraperitoneally into BALB/c mice, the cells initially undergo a marked reduction in the proportion of PFC/10(6) followed by a return of PFC to pretransfer levels by 7-10 days. Hapten-conjugated mouse IgG (DNP-MGG), which induces tolerance to DNP in normal mouse B cells, also induces suppression of HC PFC when administered within the first 2 days after the transfer. Administration of tolerogen either 2 days before injection of HC or after the PFC response has returned to preinjection levels fails to give suppression. Suppression is dose dependent and hapten specific since immunogenic hapten-carrier conjugates (e.g., DNP-KLH, DNP-Ficoll) and fluorescein-MGG are not suppressive. T cells may not be required for suppression since hybridoma cells inoculated into nude mice are also suppressed by DNP-MGG. These results suggest that hybridoma cells undergo a change from nonsecreting to secreting cells during in vivo growth and that administration of tolerogen during the nonsecreting stage inhibits antibody secretion.

Animals↗
PubMed1983

A prospective analysis of the arthritis syndrome and immune function in jejunoileal bypass patients.

Fifty-two patients undergoing jejunoileal bypass surgery were prospectively evaluated to determine: 1) the incidence of the associated arthritic syndrome; 2) whether we could identify patients at risk for arthritis prior to surgery; and 3) changes in immune function. The incidence of arthritis was 28% and was frequently associated with dermatitis. No preoperative clinical or laboratory parameters identified those patients at risk to develop rheumatic problems. Circulating immune complexes were found in both arthritis and non-arthritis patients after surgery. Mean serum levels of IgA rose significantly after surgery only in patients who developed arthritis, but remained within the normal range. No other immunologic abnormalities were noted.

Adult↗
PubMed1982

SAA suppression of immune response in vitro: evidence for an effect on T cell-macrophage interaction.

SAA has been shown previously to inhibit the in vitro antibody response of normal murine spleen cells to SRBC. This effect is nonspecific but does not directly suppress B cells. To evaluate the mechanisms of this suppression, the in vitro antibody response to SRBC was studied using cells from cytoxan-treated mice. No evidence for preformed suppressor cells was found. Also, preincubation of normal cells with SAA failed to reveal evidence for the generation of suppressor cells in vitro. The addition of 2-mercaptoethanol to cultures completely reversed the suppression caused by SAA. Addition of either normal T cells or normal macrophages to cultures partially reversed suppression caused by SAA, but only a combination of T cells and macrophages could completely reverse the suppression. These data are consistent with an effect of SAA on macrophage-T cell interaction in the generation of the immune response to T-dependent antigen. No evidence for the participation of suppressor cells as has been demonstrated for alpha-fetoprotein was found.

Amyloid↗
PubMed1981

The effect of cyclic nucleotides on tolerance induction by dinitrophenyl-isologous immunoglobulin G.

When tolerance to a hapten is induced by injecting the hapten conjugated to isologous immunoglobulin (Ig) G (dinitrophenyl (DNP)-IgG), the hapten remains on the surface of the antigen binding cell (ABC) for the duration of the tolerant state. Although this has been interpreted as a receptor blockade of ABC, it does not necessarily indicate that physical blocking of antigen receptors is the only mechanism of tolerance. Data are presented which suggest that cyclic nucleotides play a role in the in vitro induction of tolerance by DNP-IgG. Agents that elevate intracellular cyclic adenosine 3',5' monophosphate (cAMP) levels were added to lymphocytes during tolerance induction in vitro by DNP-IgG. Dibutyryl cAMP, theophylline, aminophylline, and isobutyl alpha-methylxanthine were able to inhibit the induction of tolerance to DNP. On the other hand, addition of dibutyryl cyclic guanosine 3',5'-monophosphate (cGMP) to lymphocytes incubated with doses of DNP-IgG that ordinarily are too low to induce tolerance facilitated tolerance induction. The possible role of these intracellular second messengers in the induction to tolerance is discussed.

Aminophylline↗
PubMed1981

Suppression of in vitro antibody response of human peripheral blood lymphocytes by a heat-labile factor in normal human serum.

When fresh autologous serum was added to normal human peripheral blood lymphocytes (PBL), it suppressed greater than 90% of the in vitro anti-SRBC response of these cells. Heating the serum for 30 min at 56 degrees C reversed this suppression, Serum from a patient with rheumatoid arthritis and circulating immune complexes had no suppressive effect on the anti-SRBC response of normal human PBL, but serum from patients having the same disease, without circulating immune complexes, did suppress over 90% of the plaque-forming cell response. Serum from an agammaglobulinaemic patient was also suppressive. Addition of serum from patients with congenital deficiencies of C2, C3, C5 and C8 also has a suppressive effect. Absorption of normal serum with immune complexes markedly decreased levels of C1 and C4, and also reversed the suppressive effect of this serum. These data suggest that a heat-labile factor in normal human serum which can be absorbed by immune complexes suppresses the antibody response to a T-dependent antigen. Other immune suppressors found in normal human serum are heat-stable or do not suppress in the presence of normal serum proteins. Thus the suppressive protein described in these studies may be unique. It is possible that either C1 or C4 or both may play a role in the suppression noted here.

Agammaglobulinemia↗
PubMed1980

Methylprednisolone pulse therapy for nonrenal lupus erythematosus.

High-dose intravenous methylprednisolone therapy has previously been shown to be efficacious in the treatment of renal lupus erythematosus. The present report presents 2 patients with life-threatening, nonrenal lupus erythematosus. One patient had coma and seizures, while the other had sever thrombocytopenia and anaemia. Both had failed to respond to oral corticosteroid therapy in high doses but had dramatic clinical responses with intravenous methylprednisolone given in 'pulses.' Possible mechanisms of clinical improvement are discussed.

Adult↗
PubMed1979

Antigen-specific suppressor cells in hapten-specific carrier-determined tolerance.

Tolerance to the hapten 2,4-dinitrophenyl (DNP) induced by the injection of DNP coupled to isologous IgG (carrier-determined tolerance) is associated with a receptor blockade of antigen-binding lymphocytes. In the present study, hapten-specific suppressor cells were detected in the spleens of mice made tolerant by intravenous injection of 20 microgram DNP-IgG. When spleen cells from mice rendered tolerant to DNP were co-cultured with normal spleen cells in Marbrook cultures, the response to DNP-Ficoll was suppressed, while the response to sheep red blood cells was not altered. Depletion of T cells from these spleens restored the normal anti-DNP response. The suppressor cells were not detectable in the spleen lymphocyte population of mice in the early stages of tolerance but were present on day 7 after injection of tolerogen, and disappeared by day 14. Mice injected with larger doses of 1 mg or four weekly doses of 200 microgram DNP-IgG did not have detectable suppressor cells. Thus, it appears that a short-lived suppressor T cell is generated in carrier-determined tolerance. This cell most likely plays a minor role in the mechanism of carrier-determined tolerance and may be associated with the receptor blockade which is seen early in tolerance.

Animals↗