bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of murine spleen cells by lipid A: negative modulation of lipid A mitogenic activity by O-antigen polysaccharide.
Authors: Vukajlovich S W , Morrison D C 
Published: December 2022

Abstract
We have investigated the regulatory effects of polysaccharide-rich subunits upon lipid A activity with the use of hybrid LPS macromolecules of defined subunit composition. Hybrid LPS were constructed with polysaccharide-rich LPS from Escherichia coli O55:B5 and lipid A-rich LPS from Salmonella minnesota R595 by dissociation of the two parental LPS species to monomeric solutions with deoxycholate, admixing these LPS in various proportions and reassociation into high m.w. LPS hybrid aggregates by removal of the deoxycholate. Isopycnic densities of LPS hybrids were intermediate to those of the two parental LPS species, confirming the formation of true hybrids. Murine spleen cell proliferative responses induced by hybrid LPS macromolecules were also intermediate to those obtained with parental LPS but significantly less than would be anticipated on the basis of total lipid A content. These results demonstrate that the polysaccharide portion of LPS can negatively regulate the expression of lipid A in LPS micellar aggregates.
Production of soluble suppressor factor by spleen cells from mice immunized with type III pneumococcal polysaccharide.
Authors: Taylor C E , Baker P J 
Published: December 2022

Abstract
Supernatant fluid (SF) derived from spleen cell cultures, obtained from mice 16 hr after immunization with 0.5 microgram of Type III pneumococcal polysaccharide (SSS-III), suppressed the antibody response when SF was given (i.v.) 3 hr before immunization with SSS-III. Such suppression was antigen specific and could be reproduced by SF derived from cultures of T cells from mice immunized with SSS-III (0.5 microgram) or by SF derived from cultures of spleen cells from mice primed with a subimmunogenic dose of SSS-III (0.005 microgram). Adsorption of SF with SSS-III covalently bound to a Sepharose 4B column did not alter the ability of SF to suppress the SSS-III-specific antibody response. However, adsorption of SF with Ig+ (B) cells from mice immunized with 0.5 microgram SSS-III completely removed the suppressive activity. Significant (p less than 0.05) suppression of the antibody response was observed only when SF was administered (i.v.) 24 hr before to 24 hr after immunization with 0.5 microgram of SSS-III. These results suggest that suppressor T cells generated in response to SSS-III function by releasing a soluble factor(s) that binds to determinants on B cells rather than antigen; this soluble factor(s) acts directly on antigen-stimulated B cells or inhibits the induction of amplifier T cells.
Noncovalent association of heavy and light chains of human immunoglobulins. IV. The roles of the CH1 and CL domains in idiotypic expression.
Authors: Rinfret A , Horne C , Dorrington K J , Klein M 
Published: December 2022

Abstract
A rabbit anti-idiotypic antiserum was raised against a monoclonal human IgM kappa(Me) in order to analyze the possible modulation of idiotypic expression by Fab constant domains. IgM(Me) fragments, subunits, and domains were prepared by chemical and enzymatic cleavages. All molecular species were shown to have a well-defined secondary and tertiary structure by circular dichroism. Full recombination between domains and subunits was ascertained by difference spectroscopy. The expression of the idiotype on native and recombined fragments, domains, and subunits was quantitated in a competitive enzyme-linked immunosorbent assay (ELISA). Reduced and alkylated Fab, isolated H and L chains, purified Fv(Me), intact VH and VL domains and H-L, VH-L, VL-H, and VH-VL recombinants were compared on a molar basis to native Fab(Me) for idiotypic expression. VH-specific determinants were found, whereas the L chains were virtually devoid of idiotypic activity. Both the peptic FV(Me) fragment, which is composed of intact VH and VL domains, and the recombined VH-VL heterodimer were found to be fourfold less active for idiotype expression than native Fab(Me). However, full inhibition was achieved at high molar concentrations, suggesting that all the idiotopes present on Fab(Me) were expressed on FV(Me) but with a reduced antigenicity. Comparison of VH-L and VL-H hybrid molecules revealed that the presence of the C mu 1 domain was sufficient to restore full idiotypic expression as compared with native Fab(Me). These data support the hypothesis that the first constant domain of the mu heavy chain alters the quaternary interaction between the variable domains, and therefore modulates the expression of the idiotype through longitudinal interactions that are not affected by reduction of the inter-H-L chain disulfide bond.
T cell clones to two major T cell epitopes of myoglobin: effect of I-A/I-E restriction on epitope dominance.
Authors: Berkower I , Kawamura H , Matis L A , Berzofsky J A 
Published: December 2022

Abstract
The murine T cell response to sperm whale myoglobin was analyzed for polyclonal and monoclonal T cells. For polyclonal T cells, the immunodominant epitope included residue Glu 109 when the antigen-presenting cells expressed I-Ad, whereas a Lys 140-containing epitope was immunodominant when the antigen-presenting cells expressed I-Ed only. Monoclonal T cells specific for each epitope were derived from a polyclonal line. T cell clones specific for the Glu 109 epitope were restricted to I-Ad, whereas the clones specific for the Lys 140 epitope were restricted to I-Ed. Thus, for an antigen that can be presented in association with either I-Ad or I-Ed, the immunodominance of particular epitopes depends strongly on the restriction element used. The immunodominance of each epitope-Ia combination may be due to a limited repertoire of T cells or selective presentation of epitope and Ia by accessory cells.
Fine specificity, structure, and proteolytic susceptibility of the human lymphocyte receptor for IgE.
Authors: Peterson L H , Conrad D H 
Published: December 2022

Abstract
Properties of the Fc receptor for IgE (FC epsilon R) on cultured human B lymphoblastoid cells (RPMI 8866) were studied. Specificity for human IgE (hIgE) was demonstrated by inhibition studies with both Fc epsilon R+ intact cell and detergent-solubilized receptor preparations. No interaction of the FC epsilon R with other hIg classes or with rodent IgE was seen. In other studies, 3,3-dithiobis(sulfosuccinimidyl) propionate was used to cross-link hIgE to 125I surface-labeled 8866 cells. After detergent solubilization, the 125I receptor components were isolated by immunoprecipitation, and receptor peptides of 83 and 46 kilodalton kD were demonstrated by SDS-PAGE in the presence of reducing agents. Cross-linking performed after detergent solubilization gave identical results. Tryptic maps of the 83 and 46 kD polypeptides were identical with respect to surface-iodinated peptides; this indicates a structural homology between these components. The 83 kD component was more difficult to elute from IgE affinity columns, potentially because of an increased number of IgE binding sites per FC epsilon R molecule. Limited proteolysis studies of the purified FC epsilon R with papain and V8 protease from Staphylococcus aureus demonstrated that a 16 kD FC epsilon R fragment was rapidly produced. This component was also seen after papain treatment of intact cells, and it retained the ability to interact with anti-FC epsilon R antisera and, at least in the absence of detergent, with hIgE affinity columns. Potential relationships between the FC epsilon R and lymphokines that modulate the IgE response (IgE-binding factors) are discussed.
Purification and functional analysis of the polymorphic variants of the C3b/C4b receptor (CR1) and comparison with H, C4b-binding protein (C4bp), and decay accelerating factor (DAF).
Authors: Seya T , Holers V M , Atkinson J P 
Published: December 2022

Abstract
Four CR1 variants have been found in the normal population and are designated CR1-A (190,000 daltons), CR1-B (220,000 daltons), CR1-C (160,000 daltons), and CR1-D (250,000 daltons). In the present study, we first developed an improved chromatographic purification scheme for CR1 that does not employ a C3b affinity step. CR1 variants (A, B, and C) were then isolated, and their individual functional activity was assessed. Each possessed similar co-factor activity for I-mediated cleavage of C3(H2O), as well as for the inhibitory activity for fluid phase C3 convertases. These results indicate that, despite relatively large Mr differences, in the purified state these three CR1 variants have similar functional activities. The functional activity of CR1 was also compared with C4bp, H, and decay accelerating factor (DAF) in fluid phase assays designed to assess the inhibition of the C3 convertases and co-factor activity. On a molar basis, CR1 had approximately the same inhibitory activity as C4bp for the classical pathway convertase, and had the same as H for the alternative pathway convertase. These results indicate that CR1 encompasses the functional capabilities of both proteins. They also raise a number of interesting genetic and structural questions in regard to these complement regulatory proteins, because C4bp is thought to have multiple C4b binding domains, whereas H is reported to bind one C3b. DAF was an approximately fourfold better inhibitor of the alternative pathway convertase than CR1 or H, but was a fourfold less efficient inhibitor of the classical pathway convertase than CR1 or C4bp. The effective inhibitory capacity of DAF in these fluid phase assay systems suggests that the DAF substrate specificity is for the convertases. Fluid phase CR1 was twofold less efficient than H in serving as a co-factor for the first cleavage of fluid phase C3b, and hardly mediated the second cleavage. These data are in contrast to the co-factor activity of CR1 on a cell membrane, and provide additional evidence for the local environment being a critical modulator of the function of proteins that regulate the activation of C3.
Human follicular dendritic cells express CR1, CR2, and CR3 complement receptor antigens.
Authors: Reynes M , Aubert J P , Cohen J H , Audouin J , Tricottet V , Diebold J , Kazatchkine M D 
Published: December 2022

Abstract
The expression of complement receptors by human follicular dendritic cells (FDC) was investigated by immunohistochemical techniques by using polyclonal and monoclonal antibodies to antigenic determinants of CR1, CR2, and CR3. Upon optical immunohistochemical examination of frozen sections from human reactive lymph nodes and tonsils by a three-step immunoperoxidase technique, a strong staining of cell bodies and cytoplasmic extensions of FDC was observed in germinal centers with anti-CR1 and anti-CR2 antibodies. Staining for these antigens was also found on cytoplasmic extensions of FDC in the mantle zone and on the plasma membrane of B cells in the entire follicles. Staining of FDC with anti-CR2 antibody was more intense than that of B lymphocytes. Monoclonal antibodies directed against epitopes of the alpha-chain of CR3 weakly stained FDC in follicles in a similar pattern to that which was observed on adjacent sections with mouse monoclonal antibody KIM4 that only recognizes FDC in human lymph nodes. Immunoelectron-microscopy was performed on frozen sections of a lymph node involved with a centroblastic centrocytic B malignant lymphoma and a reactive tonsil with the use of rabbit F(ab')2 anti-CR1 antibodies and mouse monoclonal anti-CR2 antibody. All the plasma membrane of the cell body and cytoplasmic extensions of FDC in germinal centers and in the mantle zones homogeneously stained for CR1 and CR2 antigens. Fibroblastic reticulum cells were negative. The plasma membrane of tumoral B lymphocytes strongly stained with anti-CR1 and weakly stained with anti-CR2 antibodies. The presence of CR1, CR2, and CR3 on FDC is a unique surface characteristic of these cells that should optimally allow the cells to bind antigen/antibody complexes bearing any type of C3 fragment.
Alkyl-ether phosphoglycerides influence calcium fluxes into human endothelial cells.
Authors: Bussolino F , Aglietta M , Sanavio F , Stacchini A , Lauri D , Camussi G 
Published: December 2022

Abstract
Suspended or adherent human endothelial cells (HEC) treated with 5 to 100 nM 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC, platelet-activating factor) showed a marked concentration and temperature-dependent increase in calcium uptake. This effect was also elicited by some AGEPC analogs. At 10 nM, the relative potencies were AGEPC = 100; 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphoric acid (AGEPA) = 52.9; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphoethanolamine (AGEPE) = 20; 1-O-octadecyl-2-deoxy-2-acetamido-sn-glycero-3-phosphocholine (2-acetamido-analog)-inactive at 100 nM = 25; 1-octadecyl-2-methoxy-sn-glycero-3-phosphocholine(2-methoxy analog)-inactive, and at 100 nM = 50. 1-O-octadecyl-2-lyso-sn-glycero-3-phosphocholine(lyso-GEPC) (100 nM) was inactive. The increase in calcium uptake was accompanied by a rise in membrane-associated calcium. The ratio between nonmembrane-bound intracellular calcium and membrane-associated calcium was constant for all agonists. CV-3988, a specific AGEPC antagonist, inhibited the effect of AGEPC. Preexposure of adherent HEC to AGEPC inhibited calcium uptake upon subsequent stimulation, suggesting a deactivation of the putative receptor. AGEPC (5 to 100 nM), but not lyso-GEPC, also stimulated calcium-efflux from calcium-preloaded, adherent HEC. AGEPC and 2-acetamido-analog, at concentrations able to induce calcium influx, did not elicit the production of 6-keto-PGF1 alpha.
Protection against 17D yellow fever encephalitis in mice by passive transfer of monoclonal antibodies to the nonstructural glycoprotein gp48 and by active immunization with gp48.
Authors: Schlesinger J J , Brandriss M W , Walsh E E 
Published: December 2022

Abstract
The protective capacity of antiviral antibodies has generally been considered to depend on their interactions with structural components of the virion. Here we report protection against lethal 17D yellow fever virus (YF) encephalitis of mice by passive administration of nonneutralizing monoclonal antibodies to a 17D YF-specified nonstructural glycoprotein, gp48, and by active immunization with purified gp48. Among five anti-gp48 monoclonal antibodies tested, two with high titer complement-fixing (CF) activity were protective, whereas three antibodies with little or no CF activity were not. The ability of antibodies to protect correlated with their ability to promote complement-mediated cytolysis (CMC) of 51Cr-labeled 17D YF-infected mouse neuroblastoma (Neuro 2a) cells. Purified gp48, prepared from lysates of 17D YF-infected Vero cells by immunoaffinity chromatography, was shown to bear both YF type-specific and flavivirus group-reactive determinants in a solid phase radioimmunoassay. Immunization of mice with purified gp48 resulted in solid protection in the absence of detectable anti-virion antibody, measured by neutralization and radioimmunoprecipitation assays. The results are consistent with plasma membrane expression of gp48 and susceptibility of 17D YF-infected neural cells to CMC, a possible mechanism of host defense in 17D YF encephalitis. Protection provided by immunization with gp48, which bears a group-reactive determinant and is highly conserved among flaviviruses, may have implications in regard to flavivirus vaccine design.
The regulation of membrane-bound and secreted alpha-chain biosynthesis during the differentiation of the B cell lymphoma I.29.
Authors: Sitia R , Rubartelli A , Kikutani H , Hammerling U , Stavnezer J 
Published: December 2022

Abstract
The regulation of the synthesis of membrane-bound and secreted IgA was investigated in the murine B lymphoma I.29 during the differentiation from IgA-bearing lymphocytes to IgA-secreting cells, as caused by treatment with lipopolysaccharide (LPS). LPS induced a threefold to fivefold increase in the amount of IgA synthesized, and induced a shift from the synthesis of the membrane form of alpha-chain (alpha m) to the synthesis of the secreted form of alpha-chain (alpha s), resulting in a 60-fold increase in the amount of IgA secreted. In vitro translation of sucrose gradient-fractionated RNA indicated that two mRNA molecules, 3.1 and 2.1 kilobase pairs (kb), encode alpha m-chains, whereas a smaller RNA molecule, 1.7 kb, encodes alpha s. Analyses by RNA blotting showed that the relative amounts of the three alpha mRNA changed rapidly during LPS-induced differentiation. The amount of the 3.1 and 2.1 kb alpha mRNA decreased, and the amount of the 1.7 kb alpha s mRNA increased in LPS-stimulated cells as compared with controls. These observations suggest that the regulation of alpha m/alpha s synthesis is controlled mostly at the pretranslational level.
Immunochemical analysis of the modulation of human melanoma-associated antigens by DNA recombinant immune interferon.
Authors: Giacomini P , Imberti L , Aguzzi A , Fisher P B , Trinchieri G , Ferrone S 
Published: December 2022

Abstract
By utilizing the human melanoma cell line Colo 38, a panel of monoclonal antibodies, and a combination of serologic and immunochemical assays, the effect of recombinant immune interferon (IFN-gamma) on the synthesis, expression, and shedding of a cytoplasmic melanoma-associated antigen (MAA) and of the membrane-bound high m.w. MAA (HMW-MAA), 115K MAA, and 100K MAA has been investigated. IFN-gamma increased the synthesis and shedding of the cytoplasmic MAA, but reduced the synthesis and cell surface expression of the HMW-MAA and of the 100K MAA. The cell surface expression of the 115K MAA on IFN-gamma-treated melanoma cells was reduced, although its synthesis was not markedly changed. The effects were dose-dependent and were related to the incubation time of cells with IFN-gamma. Among the three membrane-bound MAA analyzed, the 100K MAA was the most susceptible to modulation by IFN-gamma. The effects of IFN-gamma preparations are not mediated by contaminants in IFN-gamma preparations because removal of IFN-gamma by affinity chromatography on anti-IFN-gamma monoclonal antibodies abolished its modulating activity. The effects of IFN-gamma on the cytoplasmic MAA are similar to those of leukocyte and fibroblast interferons, whereas those on the membrane-bound MAA are significantly different. The potential implications of the marked changes in the antigenic profile of melanoma cells treated with IFN-gamma are discussed in view of the changes in the immunogenicity of IFN-gamma-treated melanoma cells.
Antibodies from patients with drug-induced and idiopathic lupus erythematosus react with epitopes restricted to the amino and carboxyl termini of histone.
Authors: Gohill J , Cary P D , Couppez M , Fritzler M J 
Published: December 2022

Abstract
The sera of patients with systemic lupus erythematosus (SLE) and drug-induced lupus (DIL) were used to study the antigenic epitopes on nuclear histones that bind antibodies in these sera. ELISA and immunoblotting techniques showed that antibodies from both patient groups bound all classes of intact histone: H1 greater than H2B greater than H2A greater than H3 greater than H4. The different classes of histone were enzymatically or chemically cleaved to produce a series of peptide fragments which were then used to map the reactive epitopes by ELISA and immunoblotting. Ten of 11 DIL sera and 11 of 12 SLE sera bound the carboxy and amino terminal peptides. Only one sera of each group bound to the central hydrophobic polypeptide. The reactivity of DIL sera with fractionated histone polypeptides was similar to that observed with SLE sera. This observation suggests that the histone epitopes reacting with DIL sera are no less restricted than those reacting with SLE.
Activation, proliferation, and differentiation of circulating B cells in autoimmune thyroid disease.
Authors: Weetman A P , Volkman D J , Burman K D , Fauci A S 
Published: December 2022

Abstract
Several studies of thyroid autoantibody production in vitro have been reported with the use of pokeweed mitogen, but the conclusions that have resulted regarding the immunoregulation of B cell function in thyroid disease are difficult to interpret due to the relatively nonphysiologic nature of pokeweed mitogen stimulation. We have therefore examined the responses of circulating B cells in Graves' disease and Hashimoto's thyroiditis by using a combination of lymphokines and other stimuli that act at various stages of the B cell cycle. In patients with autoimmune thyroid disease, nonspecific B cell proliferation and differentiation into IgG-secreting cells were both normal. However, a previously unsuspected heterogeneity among patients was found in their ability to produce autoantibodies in vitro. B cells of certain patients produced maximal autoantibody in response to pokeweed mitogen, some in response to Staphylococcus aureus Cowan strain I, and some in response to the lymphokines contained in the supernatants of stimulated T cell cultures. There was no correlation between serum autoantibody levels and those achieved in vitro. Attempts to stimulate antibody production by autoantigen (thyroglobulin) were unsuccessful, even when B cells were cultured with purified autologous OKT4+ T cells to avoid potential suppressor effects in the OKT8+ population. However, OKT4+ T cells enhanced pokeweed mitogen-driven autoantibody production. Our results show that several different functional stages of B cells exist in the circulation of patients with autoimmune thyroid disease, and that circulating B cells from such patients do not manifest a uniform response to B cell stimulators. This is presumably the result of differences in migration of circulating B cells and in their level of activation at the major sites of autoantibody production, such as the thyroid gland itself. In the light of these findings, caution is required in interpreting the results obtained from studies of circulating B cells as a means of elucidating the pathophysiology of autoimmune thyroid disease.
Murine leukemic cells inhibit IL 2 production by susceptible syngeneic splenocytes.
Authors: Jenski L J , Ledford T 
Published: December 2022

Abstract
BALB/c mice fail to mount significant cell-mediated immunity against the syngeneic virally induced leukemia MCDV-12, and die approximately 10 days after tumor inoculation. Our studies in vitro demonstrated that BALB/c splenocyte and irradiated MCDV-12 cell co-culture led to reduced alloreactivity, including depressed interleukin 2 (IL 2) production. Tumor-induced immune suppression was genetically restricted, antigen nonspecific, and alleviated in part by exogenous IL 2 administration in vitro. Furthermore, mitogen stimulation of IL 2 production, not requiring self or alloantigen recognition, was unaffected by MCDV-12 exposure. These results indicate that tumor cells may escape from immunosurveillance by reducing IL 2 production in the immediate tumor vicinity, and suggest a potential role for major histocompatibility complex antigens in the immunosuppression mechanism.