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Direct antibody-sensing membrane electrodes have been developed by immobilizing ion-carrier immunogen conjugates in a liquid membrane matrix. The resulting potentiometric probes measure specific antibodies with high selectivity over nonspecific antibodies in the physiological pH range. The electrode response is shown to arise from the selective interaction of the antibody with the membrane-bound immunogen.
Variant cell lines (LC1, LC2) obtained by growth of mouse L cells (L) in cytostimulatory and cytotoxic doses, respectively, of rabbit anti-L cell antiserum AL) were found previously to be altered in many ways relative to the parent cell line. A major change was the reduction of those surface membrane antigens that AL recognizes. These cell variants have now been found to have increased membrane sialic acid relative to L. Treatment of intact variant cells with neuraminidase (50 units/ml, 37 degrees C, 1 hr) greatly restored the susceptibility of LC1 to lysis with AL. In the presence of 1/100 dilution of AL and 5% complement the viability indices (1.00 = no cell kill) of untreated and neuraminidase-treated cells were respectively: L 0.10 and 0.03 and LC1 0.91 and 0.40. Neuraminidase-treated LC2 cells retained their resistance to AL. Parallel studies with 125I-ALIgG showed increased binding to neuraminidase-treated LC1 relative to native LC1. These findings suggest that the altered membrane sialic acid content affects the immunologic behavior of this cell variant by masking the original cell surface antibody-binding sites. This represents a possible mechanism for tumors to escape immunologic control.
Priming with haptenic determinants can augment the antibody response to a new haptenic determinant presented on a different carrier to which the original haptens are also coupled. This augmentation may be accompanied by a slight increase in the affinity of the antibody formed. However, only if the test hapten is present on the original priming antigen is there a selection for high affinity antibody-forming cells and a marked increase in the affinity of the antihapten antibody produced upon boosting is seen. The data are consistent with the assumption that antibody affinity is primarily controlled by the selection of B lymphocytes by antigen, while additional factors may be involved in controlling the magnitude of the response.
Amount and affinity of anti-beta-D-galactosidase-activating antibodies (AAb) were studied in two lines of mice obtained by selective breeding for antibody response to heterologous erythrocytes. These lines, referred to as high (H) and low (L) lines, differ also in their responses to many antigens. Concerning AAb amounts, the maximal titer in H mice is higher than in L mice. However, the AAb levels in H mice decreased with increasing immunizing doses and became lower than in L mice for the highest dose. This fact can be explained in terms of intramolecular competition or suppression. Whereas the usual maturation pattern was observed in H mice, no AAb of high affinity were found in L mice, even after a minimal immunizing dose. At any dose tested, no maturation of AAb occurred until three months after immunization. This deficiency may be ascribed to B lymphocyte or macrophage modifications. A correlation between the deficiency of high-affinity AAb in L mice and their genetically induced low antibody responsiveness cannot be proved.
A 5 years old child with selective antibody deficiency having slight hypogammaglobulinaemia of the IgG-class, normal IgM and absence of IgA has been described. The patient had no isoagglutinins and no heteroagglutinins against rabbits. Antibodies of the IgG-class could be detected in a very low concentration. The child had repeated severe infections, f. e. 5 attacks of pneumonia. After diagnosis of selective antibody deficiency syndrome had been made, he has been treated with high dose gammaglobulin therapy every 4 weeks. The child did not have any severe infections since that time. Diagnostic and therapeutic possibilities in patients with selective antibody deficiency were discussed.
In Texas in 1976 and 1977, Rio Grande turkeys (Meleagris gallopavo intermedia) from seven counties and Eastern turkeys (M. g. silvestris) from one county were tested for antibodies to selected poultry pathogens. Standardized serological tests disclosed reactors to Salmonella pullorum (2.4%), S. typhimurium (2.3%), and Mycoplasma gallisepticum (4.8%). There were no reactors to Newcastle disease virus or Chlamydia psittaci. Prevalence of M. gallisepticum antibody in wild turkeys was significantly higher for counties with commercial turkey operations than for counties lacking domestic turkeys, whereas the incidence of S. pullorum and S. typhimurium did not differ significantly.
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PURPOSE: To characterize the prevalence and distribution of Dectin-2-positive macrophages across human tumors and develop a research immunohistochemistry (IHC) assay to assess Dectin-2 in cancer tissues. MATERIALS AND METHODS: C-type lectin domain family 6 member A (CLEC6A), the gene encoding Dectin-2, was evaluated across 38 tumor types using The Cancer Genome Atlas. A fit-for-purpose Dectin-2 IHC assay was developed using a monoclonal antibody selected from screening 11 anti-Dectin-2 antibodies. Assay performance was supported by Dectin-2-expressing and parental cell line controls, macrophage-associated staining patterns, and comparison with an orthogonal CLEC6A in situ hybridization method using RNAscope. Dectin-2 expression was assessed in tissue microarrays (n = 553 samples) across 6 cancer types and whole tissue sections (n = 137) across 7 cancer types. RESULTS: The Cancer Genome Atlas analysis identified enriched CLEC6A expression in several tumor types, including non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), and subsets of head and neck cancer (HNC) and colorectal cancer (CRC). By IHC, Dectin-2-positive macrophages were detected across tumor types, with notable heterogeneity within and across cancer types. In tissue microarrays, NSCLC showed the highest frequency of Dectin-2-positive macrophage infiltration, with 38% of cases with staining ≥1% of tumor area. Whole tissue section analysis confirmed and expanded these findings, with ≥50% of NSCLC, melanoma, HNC, TNBC, and CRC samples showing Dectin-2-positive macrophages in ≥1% tumor area. CONCLUSIONS: Dectin-2 expression was observed in subsets of tumor-associated macrophages across multiple human cancers, with relatively enriched expression in NSCLC, melanoma, HNC, TNBC, and CRC. To our knowledge, this study represents the first broad protein-level characterization of Dectin-2 across multiple human tumor types, identifies cancers with relatively enriched Dectin-2-positive macrophage infiltration, and provides a foundation for future translational studies of Dectin-2-targeted therapies.
Inoculation of A/J mice with syngeneic thymocytes conjugated with specifically purified A/J anti-phenylarsonate (anti-Ar) antibodies, selectively suppressed the subsequent synthesis of those anti-Ar antibodies which carry the major cross-reactive idiotype. High titers of anti-Ar antibodies were produced upon subsequent immunization but in most mice the idiotype was undetectable. Suppression similarly occurred in F1(A/J X BALB/c) and in C.AL-20 mice. Although some mice were suppressed when unconjugated antibody was injected, the suppressive effect was much more pronounced, particularly in the F1 and C.AL-20 recipients, when the antibody was coupled to thymocytes. The state of suppression could be adoptively transferred with T cells to mildly irradiated syngeneic recipients. A population enriched for B cells had little if any suppressive effect. There was no requirement for antigen in the generation of suppressors. Thymocytes conjugated with antibody did not induce idiotype-specific suppression in mice that had been recently challenged with antigen. Thymocytes from BALB/c and C57BL/10 mice were effective carriers for the anti-Ar antibodies, i.e., there was no evidence for H-2 restriction. The experiments demonstrate the feasibility of suppressing idiotype production and generating idiotype-specific suppressor T cells without the use of anti-idiotypic antibody or antigen.
Low doses of highly purified anti-TNP (trinitrophenyl) antibody specifically stimulated nucleoside uptake in TNP-substituted L cells and low doses of heterospecific anti-L cell antibody stimulated nucleoside incorporation, DNA synthesis, and cell growth in L cells in vitro. High concentrations of antibody inhibited these processes. Complement activated through C3 augmented the cytostimulatory effects of low concentrations of antibody and activated through C9 augmented the cytoinhibitory effects of antibody. One very early effect of cytostimulatory concentrations of antibody is activation of membrane carrier transport systems as seen with 45Ca2+ uptake. Growth of L cells in tissue culture in the continuous presence of a cytostimulatory concentration of antibody selected for a variant cell line that was less responsive to antibody, thought to be due to a blocking effect of increased amounts of sialic acid. In vivo experiments documented that the same antibody could modulate L cell tumor growth in T cell-depleted mice, depending on whether a low or high concentration of antibody was given passively. In the experimental systems used, therefore, antitumor antibody and complement directly modulate the growth of tumor cells.
These studies suggest that the immunologic indicator in the radioimmune assay, 125I-iodoinsulin, selects antibody populations from within the antiserum that interact with determinants distant from the solvent surface on the insulin molecule to which iodine is substituted. Evidence is presented that the connecting peptide of proinsulin is in close proximity to regions on the solvent surface of the A-chain of insulin that include the tyrosyl residues at A-14 and A-19. A marked immunologic cross-reaction between derivatives of insulin with perturbations in the regions of tyrosyl A-14 and A-19 was noted in the radioimmune assay employing desalanine-(B-30)-desasparagine-(A-21)-insulin antiserum. This observation is consistent with the presence of a restricted population of antibodies in such antisera that is directed toward immunologic determinants in or near the insulin dimer site. The apparent immunologic activity of insulin derivatives depends on which antibody populations from the antiserum pool can react with the immunologic indicatory employed on the one hand and on the composition of antibodies in that antiserum on the other. These studies indicate that the specificity of antibody populations in a given antiserum can be identified and their levels quantitated with several assay systems, each employing one of a variety of indicators.
Fourteen children with viral infection of the central nervous system have been examined with respect to their function of humoral immunity. Serum concentrations of immune globulins have been measured and antibody titers determined. Iso- and hetero agglutinins as well as antibodies against diphtheria, pertussis, and tetanus if the children were vaccinated have been measured. Anti viral antibodies were tested if children reported the respective infection in their history. Selective antibody deficiency have been found in three children all of whom had normal serum IgG and two elevated IgM levels. These three children showed complications in the course of infection. Nine children had elevated serum IgM and titers of IgM-antibodies were also in or above the high normal range.
The near-ultraviolet circular dichroism (CD) of three homogeneous anti-type III pneumococcal antibodies in the absence and the presence of the specific hexasaccharide ligand was studied. In addition recombinations and hybridizations of H and L chains derived from two of these antibodies were carried out and the CD spectra of bound and free reconstituted IgG molecules were measured. The results indicate that the CD spectra of the native antibodies in the 260-310-nm range are very similar in shape and sign and exhibit a positive band at 285 nm. The homologous reconstituted antibody molecules exhibited CD spectra very similar in shape and sign to those of the native antibody molecules although recombinant molecules are no longer stabilized by interchain disulfide bonds. Upon addition of the hexasaccharide ligand, a significant decrease in amplitude of the CD spectra (18-21%) occurred in all three native antibodies and their Fab fragments as well as in the homologous recombinant molecules. No CD spectral changes could be detected upon interaction of the hapten ligand with the heterologous recombinants. All homogeneous antibodies studied exhibited fluorescence quenching upon oligosaccharide binding and a blue shift of the emission maximum. This property allowed the determination of the binding constant of one selected antibody to be made. Taken together, CD and fluorescence spectroscopic data suggest that oligosaccharide ligands induced detectable conformational changes in the Fab fragment of the antibody.
Antibodies specific to protein HMG-1 were purified by affinity chromatography on Sepharose columns to which HMG-1 was covalently bound. Immunofluorescence studies with these antibodies reveal that HMG-1 or components which immunologically cross-react with HMG-1 are present in the cytoplasm of Chinese hamster V-79, rat liver TR-12 and bovine trachea EBTr-NBL-4 cells. At selected antibody concentrations, the fluorescence present in the cytoplasm is more intense than that observed in the nucleus. The presence of HMG-1 protein in the cytoplasm of rat liver cells was verified by direct examination of the protein content of selected cytoplasmic fractions. A protein with electrophoretic mobility identical to HMG-1 was detected by electrophoresis on polyacrylamide gels containing either sodium dodecylsulfate or urea. Furthermore, the cytoplasmic extracts yielded a positive complement fixation with anti-HMG-1, while no reaction was obtained with control anti-H1 sera. We suggest that HMG protins, rather than functioning in the nucleus alone, are important structural elements of the entire cell.