bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental autoimmune encephalomyelitis mediated by T lymphocyte lines: genotype of antigen-presenting cells influences immunodominant epitope of basic protein.
Authors: Beraud E , Reshef T , Vandenbark A A , Offner H , Friz R , Chou C H , Bernard D , Cohen I R 
Published: December 2022

Abstract
Lewis rats are susceptible to experimental autoimmune encephalomyelitis (EAE), and their T lymphocytes recognize epitopes in the 68-88 sequence of guinea pig myelin basic protein (BP). BN rats are resistant to EAE, and their T lymphocytes recognize epitopes outside of the 68-88 sequence, probably in the 43-67 portion of BP. To investigate the influence of the genome of antigen-presenting cells (APC) on the dominance of BP epitopes for T lymphocyte lines, we selected anti-BP lines from (Lewis X BN)F1 rats by using the APC of Lewis, BN, or F1 origin. We now report that the F1/Lewis and F1/F1 lines recognized the 68-88 epitopes and were highly encephalitogenic in F1 rats, whereas the F1/BN line recognized the 43-67 epitopes and was only weakly encephalitogenic. Thus, the genotype of the APC can influence the immunologic dominance for T lymphocytes of BP epitopes, and this dominance in turn can influence the expression of disease.
A transferrin receptor antibody represents one signal for the induction of IL 2 production by a human T cell line.
Authors: Manger B , Weiss A , Hardy K J , Stobo J D 
Published: December 2022

Abstract
We previously demonstrated a two-signal requirement for the activation of the human T cell lines Jurkat and HUT 78. Interleukin 2 (IL 2) production by these lines can be induced by phytohemagglutinin (PHA), T3 antibodies, or calcium ionophores, but only in combination with phorbol myristate acetate (PMA). To obtain further information about surface structures involved in T cell activation, we produced a monoclonal antibody that could substitute for PMA in the activation of HUT 78. This antibody, designated J64, induced IL 2 secretion by HUT 78 in combination with PHA, T3 antibodies, or calcium ionophores, however not by itself. J64 also had other PMA-like effects on HUT 78, such as an increase in IL 2 receptor expression and an inhibition of cell growth. J64 was shown to immunoprecipitate the transferrin receptor (TfR). However, it bound to an epitope different from those recognized by other TfR antibodies and different from the transferrin-binding site. In addition, other previously described TfR antibodies did not, like J64, function as activating stimuli for HUT 78. Possible mechanisms for activation signaling in T cells involving the TfR are discussed.
Endocytosis of aggregated immunoglobulin G by rat basophilic leukemia cells; rate, extent, and effects on the endocytosis of immunoglobulin E.
Authors: Rivera J , Mullins J M , Furuichi K , Isersky C 
Published: December 2022

Abstract
Rat basophilic leukemia (RBL) cells have distinct receptors for IgE and IgG. We assessed the endocytosis of chemically and immunochemically cross-linked mouse-IgG and its influence on the simultaneous endocytosis of IgE. We found that at 37 degrees C, aggregates of IgG and IgE were endocytosed at about the same rate with one-half of the maximal endocytosis occurring in 5 to 13 min, and the efficiency of endocytosis for both ligands ranging from 40 to 70%. We also found that endocytosis of cross-linked IgE and IgG occurred simultaneously and neither ligand significantly affected the rate or extent of endocytosis of the other. The cells accumulated the cross-linked IgG, and then released it to the extracellular environment, at a rate (less than 3%/hr) slower than the released endocytosed IgE (greater than 10%/hr). Using an assay that discriminates between unbound and receptor-bound oligomeric IgG, we found that oligomeric IgG is endocytosed with its receptor, and that the bulk of the ligand remains bound to its receptor for greater than 120 min after endocytosis. The differences in the rate of release of endocytosed IgG vs IgE suggests that the intracellular fate or pathway of these two oligomeric ligands may differ.
Autoantibodies to creatine kinase in rabbits infected with Treponema pallidum.
Authors: Strugnell R A , Williams W F , Raines G , Pedersen J S , Drummond L P , Toh B H , Faine S 
Published: December 2022

Abstract
Sera from rabbits infected intratesticularly with Treponema pallidum (Nichols) for 30 days were examined for autoantibody reactivity against muscle and testis extracts by Western immunoblotting. Syphilitic sera (30 day) reacted with an autoantigen of 43,000 daltons in muscle extracts. The antigen was shown to be creatine kinase (CK). Studies with the use of an anti-CK ELISA showed that the autoantibody to CK first appeared 3 wk after infection, declined by 7 wk infection, and was absent in rabbits "mock"-infected with heat-killed T. pallidum. CK activity was not detected in sonicated or intact, washed T. pallidum, suggesting that the antibody was not produced in response to treponemal CK.
In vivo or in vitro selection for resistance to natural cytotoxic cell lysis selects for variants with increased tumorigenicity.
Authors: Patek P Q , Lin Y , Collins J L , Cohn M 
Published: December 2022

Abstract
Experiments were designed to test the hypothesis that transformed cells that are NC sensitive must escape NC activity if they are to grow as tumors in normal individuals. NC-resistant variants were selected either in vivo or in vitro from NC-sensitive cell lines that grow as tumors in immunodeficient mice but not in syngeneic normal mice. The tumorigenicity of cloned NC-resistant variants was compared with the parental cell lines and to cell lines that went through the selection procedure, but after cloning remained NC sensitive. Cloned NC-resistant cell lines derived from tumors that developed in x-irradiated nude mice after the injection of an NC-sensitive cell line are tumorigenic in normal mice, whereas cloned NC-sensitive cell lines derived from the same tumors are unable to grow as tumors in normal mice. Similarly, six of seven NC-resistant cloned cell lines independently isolated after in vitro selection for NC-resistance are tumorigenic in normal mice, whereas cloned NC-sensitive cell lines isolated from the same in vitro selected populations are not tumorigenic in normal mice. Thus, either the in vivo or in vitro selection of NC-resistant cells selects for cells tumorigenic in normal mice; these findings, along with our previous observations that selection for cells tumorigenic in normal mice selects for NC resistance, provide compelling evidence that escape from NC activity is required before some transformed cells can grow as tumors in normal mice.
Abortive activation of B lymphocytes by monoclonal anti-immunoglobulin antibodies.
Authors: Cambier J C , Heusser C H , Julius M H 
Published: December 2022

Abstract
Toward a better understanding of the signaling role of antigen-mIg binding in the generation of humoral immune responses, we have assessed the effects of soluble, monoclonal anti-Ig antibodies on various cell physiologic parameters known to change during B cell activation. These parameters include membrane potential, I-A antigen expression, narrow angle light scattering properties (size), and cell cycle state. Results indicate that all monoclonal antibodies that bind cell to surface IgM or IgD, or both, induce virtually all small B cells to undergo membrane depolarization and increased I-A expression. Only a small subset of these antibodies, exemplified by b-7-6 anti-mu, induce all small B cells to enter G1. An increasingly smaller proportion of these cells traverse each subsequent cell cycle phase, with 10% of cells reaching G2 or M phases by 60 hr of culture. The kinetics of this response to b-7-6 are considerably slower than those of the response induced by LPS. Finally, analysis of Percoll density-fractionated cells revealed that although B blasts made by b-7-6 stimulation of small cells remain b-7-6 responsive, natural B blasts isolated from the spleen are refractory to monoclonal anti-Ig stimulation as indicated by membrane depolarization, increased IA expression, blastogenesis, and [3H]thymidine uptake.
Antigenic modulation of human myotube acetylcholine receptor by myasthenic sera. Serum titer determines receptor internalization rate.
Authors: Tzartos S J , Sophianos D , Zimmerman K , Starzinski-Powitz A 
Published: December 2022

Abstract
Antibodies to the acetylcholine receptor (AChR) added to AChR-bearing muscle cells cross-link the receptors, thus increasing their internalization and degradation rate (antigenic modulation). This mechanism contributes to AChR loss in myasthenia gravis. Until recently, antigenic modulation has been studied in animal tissues, where only a small fraction of human anti-AChR antibodies bind. In the present study, we examined the antigenic modulation of AChR by using patients' sera and cultures of human muscle cells. We aimed to see whether antigenic modulation correlates better with disease severity or with antibody titer. Antibody-containing sera from 29 myasthenic patients in various states of the disease and with different antibody titers against AChR were tested. Control sera from six healthy individuals were also tested. Our experiments showed that all myasthenic sera affected the overall AChR content on the human myotube surface, causing a 49 to 82% loss, whereas control sera had no effect. Although at fixed serum volumes there was some correlation between disease severity and AChR loss, this effect was clearly due to differences in antibody titers. In fact, the antigenic modulation depended mainly on the final concentration of the antibody present. Thus, intrinsic factors other than antibodies to AChR may determine or influence the patients' susceptibility to the disease.
Modulation of IgM anti-lymphocyte antibody-reactive T cell surface antigens in systemic lupus erythematosus.
Authors: Winfield J B , Shaw M , Minota S 
Published: December 2022

Abstract
Cold-reactive lymphocytotoxic autoantibodies are present in the serum of most patients with active systemic lupus erythematosus (SLE) and may be important for the development of the lymphopenia and T cell dysfunction characteristic of this disorder. Neither the mechanisms of autoantibody action in this regard, nor the nature of the relevant T cell membrane target molecules have been defined, however. In the present investigation, preincubation of T cells with SLE serum at 37 degrees C reduced their reactivity with SLE IgM anti-lymphocyte autoantibodies, as demonstrated by indirect immunofluorescence and complement-dependent cytotoxicity. Modulation was restricted to SLE IgM autoantibody-reactive antigen; monoclonal antibody staining of various T cell differentiation and activation antigens remained unchanged. Loss of antigen from the surface membrane was rapid, but transient. A nadir was reached after approximately 120 min of 37 degrees C incubation, followed by essentially complete reexpression of antigen several hours later. Although modulation occurred spontaneously at 37 degrees C in the absence of SLE serum, loss of antigen was enhanced by IgM anti-lymphocyte autoantibodies, despite their low thermal amplitude. Modulation was inhibited by sodium azide, by fixation of cells with paraformaldehyde, and by low incubation temperatures. Colchicine and cytochalasin D had no effect on this process, suggesting that the integrity of the cytoskeleton was not essential. Cycloheximide did not prevent loss of antigen, but inhibited its reexpression. In experiments to determine the fate of modulated antigen, both intracytoplasmic accumulation and shedding from the cell surface were demonstrated. Only shedding was increased by the presence of anti-lymphocyte antibodies, however. These studies delineate modulation of T cell membrane antigen as a new mechanism for anti-lymphocyte autoantibody action in SLE. The occurrence of modulation at physiologic temperatures in vitro suggests that a similar phenomenon of potential relevance to T cell dysfunction may obtain in patients with this disorder.
Diabetic BioBreeding/Worcester (BB/Wor) rats need not be lymphopenic.
Authors: Like A A , Guberski D L , Butler L 
Published: December 2022

Abstract
The BB/Wor rat is an animal model of spontaneous autoimmune type I diabetes mellitus. Previous reports have emphasized the presence of lymphopenia in all diabetic and diabetes-prone BB rats. This manuscript reports the appearance of diabetes among three family lines of BB/Wor animals that were previously free of diabetes. Diabetic W-line rats are not lymphopenic and possess normal percentages of phenotypic T cell subsets. Hence the presence of lymphopenia is not obligatory for the occurrence of diabetes in BB/Wor rats.
Autoimmunity induced by HgCl2 in Brown-Norway rats. I. Production of monoclonal antibodies.
Authors: Hirsch F , Kuhn J , Ventura M , Vial M C , Fournie G , Druet P 
Published: December 2022

Abstract
Mercuric chloride (HgCl2) induces in Brown-Norway rats (BN) a B cell polyclonal activation resulting in autoimmune disease. Spleen cells from BN rats injected with HgCl2 were fused with IR983F, a nonsecreting rat myeloma cell line, in order to obtain monoclonal antibodies reacting with autoantigens or IgE-producing hybridomas. After screening for immunoglobulin-producing clones, we found 5% clones with anti-tissue activity, 8% with anti-TNP activity, and 41% secreting IgE. Among the anti-tissue monoclonal antibodies, one recognizes both TNP and mesangial structures of rat normal glomeruli, which could be an as yet unrecognized mechanism of nephrotoxicity. These experiments 1) confirm that HgCl2 induces polyclonal activation, 2) show that the mercury model is of interest to obtain monoclonal IgE and various autoantibodies, and 3) suggest a new possible mechanism of antibody-mediated renal injury.
Mechanism of synergy between T cell signals and C8-substituted guanine nucleosides in humoral immunity: B lymphotropic cytokines induce responsiveness to 8-mercaptoguanosine.
Authors: Goodman M G 
Published: December 2022

Abstract
B lymphocytes require a source of T cell-like help to produce antibody to T cell-dependent antigens. T cell-derived lymphokines and C8-substituted guanine ribonucleosides (such as 8-mercaptoguanosine; 8MGuo) are effective sources of such T cell-like help. Addition of T cell-derived lymphokines to antigen-activated B cells together with 8MGuo results in synergistic B cell differentiation, amplifying the sum of the individual responses twofold to four-fold. Lymphokine activity is required at initiation of culture for optimal synergy with 8MGuo, whereas the nucleoside can be added up to 48 hr after the lymphokines with full synergy. 8MGuo provides a perceived T cell-like differentiation signal to B cells from immunodeficient xid mice, thereby distinguishing a subset of Lyb-5- nucleoside-responsive B cells from those activated by soluble anti-mu followed by B cell stimulatory factor-1, interleukin 1, and B cell differentiation factors, which are Lyb-5+. Moreover, at least a subset of the B cells recruited by the synergistic interaction of lymphokines and nucleoside is distinct from that responsive to 8MGuo + antigen, insofar as Sephadex G-10 nonadherent xid B cells fail to respond to either 8MGuo or lymphokines alone, but do respond to the combination. A distinct subpopulation can also be demonstrated among normal B cells by limiting dilution analysis in which the precursor frequency of antigen-reactive B cells in the presence of lymphokines or nucleoside alone increases substantially when both agents are present together. In concert with the kinetic data, these observations suggest that synergy derives at least in part from the ability of lymphokines to induce one or more elements the absence of which limits the capacity of a distinct B cell subpopulation to respond to 8MGuo.
Ek beta mutant antigen-presenting cell lines expressing altered Ak alpha molecules.
Authors: Quill H , Schwartz R H , Glimcher L H 
Published: December 2022

Abstract
Antigen-presenting cells (APC) expressing mutant Ek beta and Ak alpha proteins were isolated after chemical mutagenesis of TA3 cells and negative immunoselection for altered Ek beta molecules. Mutant clones were analyzed for biosynthesis, assembly, and cell surface expression of altered Ia molecules, and were assayed for antigen-presenting function by using a variety of T cell clones. Three types of mutants were detected: type 1, which had lost expression of the Ek beta chain and produced altered Ak alpha chains; type 2, which also expressed altered Ak alpha chains, and which expressed Ek beta proteins that had lost reactivity to the 17.3.3 and 74D monoclonal antibodies (mAb), but retained reactivity to other anti-Ek beta mAb; and type 3, which had lost expression of both Ek beta and Ak beta: Ak alpha surface molecules. Thus, all of the mutant clones that produced modified Ak alpha proteins also displayed either total loss or serologic modification of the Ek beta molecule. Ek beta:E alpha-reactive T cell clones were not stimulated when type 1 or type 3 cells were used as APC, but all such T cells were fully reactive with type 2 mutant APC. Most Ak beta:Ak alpha-reactive T cell clones could respond to type 1 and 2 APC, and none were responsive to type 3 APC. However, two autoreactive Ak beta:Ak alpha-specific T cell hybridomas were stimulated only very weakly by type 1 and type 2 cells expressing modified Ak alpha proteins. These results demonstrate that Ia mutations can have highly selective effects on antigen presentation to T cells as well as on mAb binding, and thus suggest that individual Ia molecules may be composed of many different functional subsites.
Allotypy of the rabbit kappa 2 light chain: evidence that the kappa 2 isotype is expressed by all members of the rabbit species.
Authors: Marrakchi R , Gaaied A B , Roland J , Cazenave P A 
Published: December 2022

Abstract
The rabbit kappa 2 light chain subtype was described after isolation of the Basilea mutant strain, which does not express the kappa 1 subtype; antibodies raised in domestic rabbits against the Basilea kappa 2 chain recognized antigenic determinants present in Basilea strain rabbits and in some wild Oryctolagus cuniculus individuals. Some authors have proposed that the kappa 2 isotype is expressed in some individuals and is silent in others. The results presented here provide immunochemical and genetic evidence that the kappa 2 isotype presents at least two allotypic forms, bas 1 (equivalent to bas+) and bas 2 (equivalent to the so-called bas-), which are expressed in low levels in all members of the rabbit species. In addition, preliminary data on the expression of the bas 2 allotype in some hares (Lepus capensis) are reported. On the basis of these results, the rules guiding the selection of kappa 1 and kappa 2 isotypic light chain expression in this species may now be approached.
Structural analysis of the epitopes recognized by monoclonal antibodies to angiotensin II.
Authors: Couraud P O 
Published: December 2022

Abstract
Six clones were obtained that secrete anti-angiotensin II antibodies after somatic cell fusions between splenocytes of immunized BALB/c or outbred OF1 mice and NS-1 myeloma cells. The dissociation constants for angiotensin II ranged from 0.3 to 2.9 nM. A panel of 20 structural analogs of the hormone were used as probes to analyze the specificity of binding. From the binding studies and the putative three-dimensional structures of the tested peptides, three families of antibodies could be distinguished that recognized overlapping epitopes; the conservation of the native conformation of the angiotensin II molecule in the analogs appeared essential for the preservation of a high affinity to the antibodies. With one antibody, the affinities of the angiotensin II analogs have been correlated with their intrinsic biologic activities (as measured by in vivo pressor tests), and not with their binding affinity to the membrane receptor. These results are interpreted as mimicry, by the antibody binding site, of the active conformation of the receptor site.
Interference of a C3-fragment preparation with IL 2-dependent proliferation.
Authors: Walker C , Kristensen F , Bitter-Suermann D , Stadler B M , de Weck A L 
Published: December 2022

Abstract
A C3-fragment preparation (C3-FP) was studied for its ability to regulate human peripheral blood lymphocyte activation. It was found that very low concentrations of this low m.w. fraction, which was free of C3a, inhibited the PHA-induced lymphocyte proliferation without any cytotoxicity. Cytofluorometric analysis showed that C3-FP did not influence the transition of T cells from the G0 to the G1a phase of the cell cycle. However, the IL 2-dependent transition from the G1a to the G1b phase of the cell cycle was effectively blocked. Addition of exogenous IL 2 did not release cells arrested in the G1a phase. Furthermore, neither IL 2 production nor IL 2 receptor formation was inhibited by C3-FP, and binding of IL 2 to its receptor was unaltered. It was found that only IL 2-dependent cell lines were inhibited in their proliferation; all other tested cell lines were unaffected by C3-FP. Our findings suggest that cleaved products of C3 may inhibit IL 2-dependent lymphocyte proliferation at a stage where the IL 2 signal is required for initiation of proliferation.
Immunomodulation by neutrophil myeloperoxidase and hydrogen peroxide: differential susceptibility of human lymphocyte functions.
Authors: el-Hag A , Lipsky P E , Bennett M , Clark R A 
Published: December 2022

Abstract
The coexistence of activated polymorphonuclear leukocytes and lymphocytes in tumor masses and inflammatory tissues suggests the possibility of interaction between secreted neutrophil products and nearby lymphocytes. To test this hypothesis, we examined the effects of neutrophil myeloperoxidase and H2O2 on lymphocytes. Human peripheral blood mononuclear leukocytes were exposed to myeloperoxidase, an H2O2-generating system (glucose + glucose oxidase), and a halide, and were then tested for functional activities. Natural killer activity against K562 cells, lymphocyte proliferation in response to mitogens, and generation of immunoglobulin-secreting cells were all susceptible to oxidative injury by myeloperoxidase and H2O2. The degree as well as the mechanism of suppression was dependent on the glucose oxidase concentration (i.e., the rate of H2O2 delivery). At low H2O2 flux, myeloperoxidase was essential for induction of lymphocyte suppression; as the rate of H2O2 generation increased, suppression became myeloperoxidase-independent and was mediated by H2O2 alone. Various lymphocyte functions were differentially susceptible to oxidative injury by myeloperoxidase and H2O2. The proliferative response to poke-weed mitogen was the least sensitive, whereas antibody formation was the most sensitive. Proliferative responses to concanavalin A and phytohemagglutinin as well as natural killer activity displayed intermediate degrees of susceptibility. In all assays, lymphocyte viability was greater than 90%. Removal of monocytes from mononuclear leukocytes by adherence to glass increased susceptibility of lymphocytes to oxidative injury. Monocytes in proportions within the range present in peripheral blood mononuclear leukocytes protected lymphocyte functions against oxidative injury by myeloperoxidase and H2O2. This study demonstrates a differential susceptibility of various immune functions to oxidative injury by the neutrophil products myeloperoxidase and H2O2, and shows, in addition, that monocytes can modulate these interactions.