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S Haba

Publications and source records attributed to S Haba.

32 records · Page 2Linked to original sources
PubMed1987

Induction of high titers of anti-IgE by immunization of inbred mice with syngeneic IgE.

We have generated high titers (up to 1 mg/ml) of antibodies to isotypic determinants of IgE by immunization of A/J mice with syngeneic monoclonal IgE conjugated to keyhole limpet hemocyanin. As much as 3 mg of anti-idiotypic antibodies per ml was induced at the same time. In contrast to conventional rheumatoid factors, the anti-isotypic antibodies are of moderately high affinity (10(7)-10(8) M-1). Assays of the anti-IgE antisera indicated the presence of IgE, both free and in the form of immune complexes; the latter values are minimum estimates owing to masking of isotypic determinants. Regulatory effects of these high titers of anti-IgE can now be investigated. Such studies will be facilitated by the availability of monoclonal, syngeneic anti-IgE antibodies.

Animals↗
PubMed1986

Inhibition of an IgE response by secondary B cells of a different isotype.

We found that the synthesis of IgE anti-Ars antibodies is strongly inhibited by the presence of secondary non-IgE-producing cells that are specific for the Ars hapten. Such B cells can be induced by inoculation of a protein-Ars conjugate in CFA. The effect is seen after inoculation of OVA-Ars in CFA followed by KLH-Ars in alum, or, more convincingly, after adoptive transfer of B cells induced by antigen in CFA. Dose-response data indicated that inhibition can be effected by B cells containing noninhibitory numbers of contaminating T cells. Possible synergistic effects of carrier-specific regulatory T cells were ruled out by using a different protein carrier for immunization of donor and recipient mice. The effect was shown to be specific for the hapten used for immunization of donor mice.

Animals↗
PubMed1986

Primary structure of IgE monoclonal antibodies expressing an intrastrain crossreactive idiotype.

We have obtained amino acid sequences (by mRNA and amino acid sequencing) for two IgE kappa mAb that have specificity for the Ars hapten group and are related to the major idiotypic family, CRIA (crossreactive idiotype A), in the A strain of mouse. One mAb, SE20.2, fully expresses CRIA; the other, SE1.3, possesses some but not all of the characteristic idiotopes. Both IgE proteins contain VH and V kappa segments that are closely related to those associated with CRIA. The D segment of SE20.2 is also typical of CRIA+ mAb, but that of SE1.3 is one amino acid residue longer. Chain recombination experiments indicated that the L chain of SE1.3 is fully capable of supporting CRIA expression. Its deficiency with respect to idiotopes of CRIA was attributed to the extra amino acid in the D region and/or substitutions in the VH segment. A major objective was to ascertain the frequency of somatic mutations in IgE. For the VH segment (amino acids 1-98) of SE20.2, there are only three nucleotide differences and one uncertainty with respect to the nucleotide sequence of the germline gene associated with CRIA. A somewhat higher frequency of substitutions is present in the VH segment of SE1.3. The VK amino acid sequences of the IgE proteins are nearly identical to those of a prototype of the CRIA family, mAb R16.7. The results are discussed with reference to the mechanism of the IgM to IgE switch.

Amino Acid Sequence↗
PubMed1986

Relationship of VH and VL genes encoding three idiotypic families of anti-p-azobenzenearsonate antibodies.

We describe here an intrastrain, cross-reactive idiotype (CRI), CRID, associated with anti-p-azobenzenearsonate antibodies of the A/J strain of mouse and distinguishable, by some but not by all of its idiotopes, from the major anti-p-azobenzenearsonate idiotype (CRIA). Molecules carrying the CRID idiotype have heavy chain variable-segment sequences that are identical or nearly identical to that of the germ-line-encoded heavy chain variable sequence of CRIA. Their light chain variable sequences are very similar to those present in a third idiotypic family, CRIC, that is a minor CRI in the A/J strain but a major CRI in BALB/c. This appears to represent a form of combinational diversity, in which the heavy and light chain variable region genes of two unrelated idiotypic families interact to form a third family, all involving antibodies of the same antigen-binding (anti-p-azobenzenearsonate) specificity. The D region of CRID, in the six monoclonal representatives studied (three IgMs, three IgGs), is unusual in that it comprises a single amino acid--arginine or serine; there are eight amino acids in the D region of CRI+A antibodies. Three different heavy chain joining regions, JH1, JH2, and JH3, are utilized. A serological reagent was developed that identifies CRID; it was used to show that the idiotype is present in relatively high concentration, comparable to that of CRIA, in anti-p-azobenzenearsonate antibodies taken soon after primary immunization. In serum taken later CRIA greatly predominates, but CRID persists at low levels.

Animals↗
PubMed1985

Quantitation of IgE antibodies by radioimmunoassay in the presence of high concentrations of non-IgE antibodies of the same specificity.

Radioimmunoassays for mouse IgE antibodies, based on adherence to an antigen-coated surface, are precise and sensitive, but errors can be introduced by the presence of relatively high concentrations of non-IgE antibodies of the same specificity. Such errors are caused by competition for the limited number of antigenic determinants on the antigen-coated surface. In this paper we explore further the quantitative aspects of the 'competition effect'. An easily applied method is described, based on preferential precipitation of non-IgE antibodies by ammonium sulfate, that permits analysis of IgE antibodies in the presence of large amounts of non-IgE antibodies (that are principally IgG). For IgE anti-Ar, the maximum permissible ratio is extended from approximately 1500:1 to at least 40,000:1. We have also determined the effect of IgG antibodies or whole mouse serum on PCA reactions of mouse IgE antibodies, carried out in rats.

Ammonium Sulfate↗
PubMed1985

Clearance of IgE from serum of normal and hybridoma-bearing mice.

The half-life of IgE in the mouse was investigated by using radiolabeled and unlabeled monoclonal antibodies of the IgE class. Quantitative serologic assays were used for the unlabeled antibodies. IgE was cleared rapidly upon i.v. inoculation; after 48 hr, less than 0.2% of the initial concentration remained in the serum. The IgE was cleared initially with a half-life of 1 to 2 hr, attaining a relatively constant value of 5 to 8 hr. The corresponding values for IgG1, determined as a control, were 11 to 12 hr and 9 to 11 days, respectively. The initial stage probably reflects equilibration with extravascular spaces. This is supported by experiments with mice in which IgE-secreting tumors were implanted and then resected; IgE was cleared from such mice with an average initial half-life of about 5 hr. The rates of clearance of inoculated IgE were approximately the same in mice bearing an IgE-secreting tumor and in normal mice. This suggests that the initial rapid clearance of IgE from normal mice is not due to adherence of IgE to saturable sites; such sites might be expected to be occupied in mice expressing high serum concentrations of IgE. This conclusion was supported by experiments in which 1-mg quantities of IgE were inoculated i.v. into normal mice daily for 6 days. Additional IgE injected on day 7 was cleared normally. The results obtained with tumor-bearing mice indicate that the reported failure to elicit an IgE response to an antigen in mice bearing IgE-secreting hybridomas cannot be attributed to rapid clearance of newly synthesized IgE in such mice, as compared with normal mice.

Animals↗
PubMed1984

Quantitative measurements of an intrastrain cross-reactive idiotype in IgE antibodies.

This paper describes the development of methods for quantitation of an intrastrain cross-reactive idiotype (CRIA) in IgE antibodies directed to the p-azophenylarsonate (Ar) group and their application to normally immunized and idiotypically suppressed mice. The data were validated by the use of monoclonal and serum anti-Ar antibodies known to possess or lack CRIA. The idiotype was absent in the IgE as well as the total anti-Ar population of idiotypically suppressed mice. A good correlation was noted between the CRIA content of total and IgE anti-Ar with a trend toward a somewhat lower content in the IgE population. Irradiated mice that received immune cells prior to further immunization expressed relatively low concentrations of the idiotype (per weight unit of anti-Ar). The method will be useful in studies of the regulation of the switch to IgE synthesis.

Animals↗
PubMed1983

Analyses of idiotypes on anti-alpha-1, 6-dextran antibodies in mice.

When mice of strains C57BL/6, C3H/He, and BALB/c were immunized with native dextran B512, only a small amount of IgM antibody was produced, but a substantial amount of anti-dextran antibody of IgG class was produced after immunization with a conjugate of dextran T10 and keyhole limpet hemocyanin regardless of the mouse strain used. Isoelectric focusing (IEF) spectra revealed limited heterogeneity of anti-dextran antibody of IgG class with strict consistency in all individual sera from C57BL/6 mice, even after secondary immunization, whereas antibodies from C3H/He and BALB/c mice showed more heterogeneous IEF spectra with some individual variations. Rabbit anti-idiotypic (Id) antibodies were raised by immunization with a subfraction of anti-dextran antibody of IgG class from C57BL/6 mice, which showed major bands focused at around pH 7.7 upon IEF. It was found by using the anti-Id antibodies that virtually all anti-dextran antibody molecules of both IgG and IgM classes from C57BL/6 mice possessed common Id determinants which can be classified into two specificities, one specific for antibody from C57BL/6 mice and the other cross-reactive with antibodies from BALB/c and C3H/He mice. About 80% of the antibody molecules from BALB/c and less than 20% of those from C3H/He mice were positive for the interstrain cross-reactive Id. Both Id determinants seemed to be closely related to the antigen binding sites, or at least to reside in the vicinity of the antigen binding sites of anti-dextran antibody.

Animals↗
PubMed1980

Stokes-Adams attacks due to acute nonspecific myocarditis in childhood.

Six patients aged between 1 to 11 years (4 females and 2 males) developed Stokes-Adams attacks with complete heart block due to acute nonspecific myocarditis. Transvenous pacing was instituted in 2 patients, but in the other 4 patients the ECG returned to normal by isoproterenol. All ECGs in complete heart block showed QRS complexes of right bundle branch block with left posterior hemiblock pattern, except for 1 which showed QRS complexes of complete left bundle branch block pattern. The ECG improved sequentially in order and left anterior hemiblock pattern of QRS complexes remained to the last during the convalescent period. Normal atrioventricular conduction returned by 2 to 24 hours in all but 1 patient who was dead and 1 of the 2 patients with shock. In another patient bifascicular block has persisted.

Acute Disease↗
PubMed1976

Selective inhibition of T lymphocyte repopulation of lymphoid organs as a mechanism of immunosuppression in tumor-bearing mice.

The mechanism of selective suppression of T-cell activity in Ehrlich tumor-bearing mice was investigated in an adoptive cell transfer system of secondary antibody responses to haptens. The induction of secondary antidinitrophenyl (DNP) antibody response after stimulation with DNP-homologous carrier (TD) of thymus-dependent DNP-carrier (TD)-primed spleen cells was markedly inhibited in tumor-bearing recipient mice, whereas the response to thymus independent DNP-carrier (TID) was intact as compared to that seen in normal recipients. However, if tumors were induced in the DNP-TD-primed donor mice and the spleen cells were assayed for responsiveness to DNP-TD in normal recipients, they generated a normal anti-hapten antibody response. After the DNP-TD-primed cells had been transferred into normal recipients and tumors had been induced in the recipients before DNP-TD-stimulation, the cells in tumor-bearers responded normally. These results indicate that the tumor-bearing state neither directly suppresses the responsiveness of primed cells nor interferes with the mechanism for antigen stimulation of primed cells. Direct measurement of recovery of transferred primed T and B cells from the spleen of tumor-bearing recipients revealed that the net recovery of T-cell activity markedly decreased, whereas the recovery of B cells in the spleens of tumor-bearing hosts was not affected or was even higher than the normal. Prevention of repopulation by T lymphocytes of lymphoid organs due to a postulated change in the microenvironment is suggested as a mechanism for the selective suppression of T-cell activity in Ehrlich tumor-bearing animals.

Animals↗
PubMed1976

Selective suppression of T-cell activity in tumor-bearing mice and its improvement by lentinan, a potent anti-tumor polysaccharide.

The cellular site of immunosuppression in Ehrlich tumor-bearing mice was analysed with particular reference to the T- and B-cell activities. The B-cell activity as measured by the anti-dinitrophenyl (DNP) antibody responses to DNP-thymus-independent carriers (TID) was not impaired in tumor-bearing mice as compared with normal mice, whereas the anti-DNP antibody response to DNP-thymus-dependent carriers (TD) and the development of helper T-cell activity to TD were markedly suppressed in tumor-bearing animals or mice pretreated with cell-free cancerous ascitic fluid. The selective suppression of T-cell response was not mediated by the generation of suppressor cell activity toward TD, which may depress the manifestation of developed helper T-cell activity. A marked suppression of T-cell response was observed when the animals were inoculated with tumor cells or injected with cancerous ascitic fluid prior to antigenic stimulation, but not when the animals were rendered tumor-bearing by such treatments after the immunization. The suppression of T-cell activity in both sarcoma 180 tumor-bearing mice and cell-free Ehrlich cancerous ascitic fluid-treated mice was prevented by treatment with lentinan, a potent anti-tumor polysaccharide. The applicability of this experimental system to the search for immunopotentiators relevant to tumor immunotherapy is discussed in the light of the preventive effect of lentinan on the suppression of T-cell response in tumor-bearing animals.

Animals↗
PubMed1976

Isolation of soluble immunosuppressive substance(s) from Ehrlich ascites tumor cell nuclei.

A potent immunosuppressive principle was isolated in a soluble form from the nuclei of Ehrlich ascites tumor cells. DNA-free preparation, obtained from the purified nuclei by homogenizing in 2M NaCl-5M urea solution and removing the dissociated DNA with LaCl3-precipitation, revealed strong activity to suppress the development of helper thymus-derived lymphocyte activity in mice. Moreover, almost all of the immunosuppressive activity originally found in the nuclear residue fraction after extraction with sodium citrate solution was recovered in 0.25 N HCl extract which mainly contains proteins. The nuclear components of tumor cells were also detected in the body fluid of tumor-bearing animals, as examined by the reactivity with a rabbit antiserum specific for some nuclear component of Ehrlich tumor cells. These results suggest that the immunosuppressive principle in the nuclei of Ehrlich tumor cells is a histone-like substance, and liberated into the body fluid from tumor cell nuclei in the tumor-bearing state.

Animals↗