bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two steps in the intracellular transport of IgD are sensitive to energy depletion.
Authors: Argon Y , Burkhardt J K , Leeds J M , Milstein C 
Published: December 2022

Abstract
The secretory pathway of murine IgD can be dissected by the use of carbonylcyanide m-chlorophenylhydrazone (CCCP), which inhibits two distinct steps of intracellular transport. The newly synthesized IgD that accumulates at the first step contains high mannose type oligosaccharides which are partially trimmed. The IgD arrested at this step is less processed than the IgD arrested by treatment with monensin. The properties of this biosynthetic intermediate are consistent with inhibition of Ig passage from the endoplasmic reticulum to the Golgi complex. A second CCCP-sensitive step exists in the biosynthesis of IgD, and is characterized by delta-chains that are resistant to endoglycosidase H and contain galactose. This indicates that this second step occurs during or after the passage through the trans-Golgi compartment. The galactose-containing oligosaccharides of the delta-chains arrested at this step do not contain fucose (as do mature, secreted delta-chains). Fucosylation is not inhibited by CCCP, nor is the secretion of fucose-containing delta-chains. These results show that terminal sugars are added to secretory IgD in at least two transport compartments, separable by their sensitivity to CCCP. The inhibition of the secretory pathway at both steps is reversible; upon removal of the drug the arrested IgD is processed normally and is secreted. The sensitivity to CCCP probably reflects transport steps that are sensitive to even partial depletion of ATP, because treatments with other inhibitors of oxidative phosphorylation yield similarly arrested Ig molecules. Thus, by using the protonophore CCCP, we demonstrate two energy-requiring steps in IgD transport which seem to be at two transitions in the secretory pathway. One step is during the passage from the endoplasmic reticulum to the mid-Golgi compartment and the other step is during Ig passage through the trans-Golgi, or subsequent transport to the cell surface.
Biochemical characteristics and partial amino acid sequence of the receptor-like human B cell and carcinoma antigen CDw40.
Authors: Braesch-Andersen S , Paulie S , Koho H , Nika H , Aspenström P , Perlmann P 
Published: December 2022

Abstract
The Ag CDw40 (p50, Bp50) is a phosphoprotein expressed on the surface of both B lymphocytes and on certain malignant cell types of nonhemopoietic origin. Antibodies to this Ag have been shown to act as a potent co-mitogen for B cells. In order to elucidate the function of this Ag, we have now investigated some of its biochemical characteristics as well as the relationship of B cell derived CDw40 to that derived from urinary bladder carcinoma (transitional cell carcinoma, TCC) cells. CDw40 from normal B cells or from the Burkitt lymphoma line Raji showed a characteristic pattern of three bands when analyzed by SDS-PAGE and Western blotting: a main band of 47 kDa, a degradation product of 43 kDa, and a dimer of 85 kDa. The dimer was disrupted by reduction with 2-ME but was reformed spontaneously from the purified monomers under nonreducing conditions. CDw40 from two bladder cancer cell lines gave a similar pattern but formed little or no dimer. Thirty amino acids of the amino terminal end of CDw40 from Raji and 22 amino acids of that from TCC cells (HU549) were sequenced. The sequences were unusually rich in cysteines and differed only in that the cysteine in position 6 in Raji CDw40 had been replaced by glutamine in HU549. In addition there were two conservative changes in positions 15 and 19. Taken together these results show that CDw40 derived from B cells or from TCC cells are the same or closely related molecules. Comparisons of the amino acid sequence and biochemical characteristics of CDw40 with proteins having receptor functions indicated a close structural resemblance of CDw40 to the nerve growth factor-receptor.
Differential IgG-binding characteristics of staphylococcal protein A, streptococcal protein G, and a chimeric protein AG.
Authors: Eliasson M , Andersson R , Olsson A , Wigzell H , Uhlén M 
Published: December 2022

Abstract
Various Gram-positive bacteria express different types of IgG-binding receptors, each of which displaying certain unique binding properties. To evaluate specificity and avidity aspects of the differential binding pattern, a set of competitive binding assays was employed, by using staphylococcal protein A (SPA), streptococcal protein G (SPG), and a chimeric protein AG. These receptors were analyzed, in a reciprocal fashion, for binding and inhibition of binding to a selected panel of polyclonal and monoclonal Ig. Results of the study reveal that a majority of the determinants on human and bovine IgG, recognized by SPA and SPG, are either coextensive or closely overlapping. Accordingly, a minor portion of the determinants appear to be unique in the sense that a particular determinant(s) is selectively identified by one of the two receptors. Binding assays involving purified Fc fragments from human IgG, suggest that SPG shows exclusive specificity for an Fab region determinant(s) not recognized by SPA, whereas the Fc determinants for SPA and SPG are identical or overlapping. Furthermore, one of the IgG subclasses of bovine origin appears to be seen by the SPG receptor only. The competition study also demonstrates that the novel chimeric protein AG receptor shows higher or equal avidity for variants of human IgG molecules compared to the best of its parental constituents. It can thus be deduced that chimeric receptors might be useful as optimized tools for immunologic applications.
The human B lymphocyte and carcinoma antigen, CDw40, is a phosphoprotein involved in growth signal transduction.
Authors: Paulie S , Rosén A , Ehlin-Henriksson B , Braesch-Andersen S , Jakobson E , Koho H , Perlmann P 
Published: December 2022

Abstract
The human B lymphocyte and carcinoma-associated Ag, CDw40, (p50, Bp50) is a receptor candidate for normal growth regulation. Interaction of mAb with this pan-B Ag, together with preactivating agents such as 12-O-tetradecanoylphorbol-13-acetate or anti-mu, deliver strong growth-promoting signals to the cells. We here demonstrate that signaling through this Ag is dependent on its aggregation on the cell surface. Thus, monovalent antibody fragments were relatively inefficient in this respect but effectively blocked stimulation by intact antibody. By using affinity purified CDw40 protein we have also demonstrated that it is antigenically distinct from other B cell-associated Ag, including the six differentiation clusters CD19 to CD24. The mAb S2C6 and G28.5, prepared by immunizing mice with human bladder carcinoma cells or tonsillar B-cells, respectively, were the only antibodies giving detectable binding. Either of these antibodies could also completely block the binding of the other, suggesting an identity or structural proximity of the epitopes recognized. The CDw40 Ag was shown to be a phosphoprotein lacking intrinsic protein kinase activity. The results provide further evidence for CDw40 being an important B cell growth factor receptor which may also have growth regulatory functions in the development of certain human carcinomas.
Expression of ets genes in mouse thymocyte subsets and T cells.
Authors: Bhat N K , Komschlies K L , Fujiwara S , Fisher R J , Mathieson B J , Gregorio T A , Young H A , Kasik J W , Ozato K , Papas T S 
Published: December 2022

Abstract
The cellular ets genes (ets-1, ets-2, and erg) have been identified by their sequence similarity with the v-ets oncogene of the avian erythroblastosis virus, E26. Products of the ets-2 gene have been detected in a wide range of normal mouse tissues and their expression appears to be associated with cell proliferation in regenerating liver. In contrast, the ets-1 gene was previously shown to be more highly expressed in the mouse thymus than in other tissues. Because the thymic tissue contains various subsets of cells in different stages of proliferation and maturation, we have examined ets gene expression in fetal thymocytes from different stages of development, in isolated subsets of adult thymocytes, and in peripheral T lymphocytes. Expression of the ets-1 gene was first detected at day 18 in fetal thymocytes, corresponding to the first appearance of CD4+ (CD4+, CD8-) thymocytes, and reaches maximal/plateau levels of expression in the thymus at 1 to 2 days after birth. The ets-2 gene expression is detected at least 1 day earlier, coinciding with the presence of both double-positive (CD4+, CD8+) and double-negative (CD4-, CD8-) blast thymocytes and reaches maximal/plateau levels 1 day before birth. In the adult thymus, ets-1 and ets-2 mRNA expression is 10- to 8-fold higher respectively in the CD4+ subset than in the other subsets examined. Higher levels of p55 ets-1 protein were also shown to exist in the CD4+ subset. Because the CD4+ thymic subset is the pool from which the CD4+ peripheral, helper/inducer T cells are derived, the ets gene expression was examined in lymph node T cells. Both the CD4+ and the CD8+ T cells subsets had lower ets RNA levels than the CD4+ thymocytes. These results suggest that ets-2 and more particularly ets-1 gene products play an important role in T cell development and differentiation and are not simply associated with proliferating cells, which are observed at a higher frequency in fetal thymocytes, or dull Ly-1 (low CD5+), and double-negative (CD4-, CD8-) adult thymocytes. Selectively enhanced expression of ets-1 gene may be observed in thymic CD4+ thymocytes because these cells have uniquely encountered MHC class II or other Ag in the thymic environment. These cells may have been subsequently stimulated to activate the ets genes in conjunction with their differentiation of helper/inducer function(s) and expression of mature TCR.(ABSTRACT TRUNCATED AT 400 WORDS)
Characterization of four homologous L chain variable region genes that are related to 6B6.6 idiotype positive human rheumatoid factor L chains.
Authors: Liu M F , Robbins D L , Crowley J J , Sinha S , Kozin F , Kipps T J , Carson D A , Chen P P 
Published: December 2022

Abstract
A significant proportion of monoclonal IgM rheumatoid factors (RF) from patients with mixed cryoglobulinemia express a KIIIa L chain-associated cross-reactive idiotype, termed 6B6.6. Previously, we reported the isolation from a patient with a monoclonal RF of a Vk gene, termed Humkv328, whose deduced amino acid sequence differs by three and seven residues from the L chains of the 6B6.6-positive RF Les and Pom, respectively. To further delineate the genetic basis of the 6B6.6 cross-reactive idiotype, we isolated from the same patient another Vk gene, termed Humkv329, which differs from kv328 by only three bases over a stretch of 1331 nucleotides sequenced. However, kv329 has a stop codon at amino acid position 94, and is thus a pseudogene. Therefore, we screened a second genomic library from an unrelated individual and isolated two potential function Vk genes (i.e., Humkv328h2 and Humkv328h5) which are highly homologous to Humkv328. All three potential functional Vk genes differ from each other by one to six bases over a 1331-bp stretch and all encode the same Vk region amino acid sequence. Among the six bases by which Humkv328h5 differs from Humkv328, two are in the conserved pentadecanucleotide region, which is known to be important in the regulation of k L chain transcription. In the future it will be important to ascertain the potential association of polymorphisms in the conserved pentadecanucleotide region with RF associated autoimmune and lymphoproliferative diseases.
Site-specific mutagenesis of the class I regulatory element the Q10 gene allows expression in non-liver tissues.
Authors: Handy D E , Burke P A , Ozato K , Coligan J E 
Published: December 2022

Abstract
Classical transplantation Ag are found on nearly all cells, whereas Ag encoded by the genes of the Qa/Tla region have a restricted tissue distribution. To investigate the cause of these different patterns of expression, we have compared the regulatory regions of Q10, a Qa region gene that is expressed only in liver, with those of H-2Ld. Gel retardation analysis shows that the nuclear factor (rI) that binds to the inverted repeat (TGGGGATTCCCCA) of the class I regulatory element (CRE) present in H-2Ld and other classical class I genes does not bind to the equivalent region of the Q10 gene. However, the Q10 CRE binds another nuclear factor (rII) that binds to the H-2Ld CRE. The sequence of the Q10 CRE differs from the sequence present in classical class I genes by three nucleotides, two of these changes are within the inverted repeat sequence (TGaGGAcTCCCCA) and disrupt the region of dyad symmetry. We have used site-specific in vitro mutagenesis to individually change these two nucleotides and have investigated the ability of this region to promote transcription with and without these substitutions. A change of either base restores transcriptional activity in chloramphenicol acetyl transferase assays and allows for binding of the rI nuclear factor. These results suggest that the failure of the Q10 CRE to bind the rI nuclear factor may play a role in preventing Q10 expression in tissues other than the liver and fetal yolk sac. Thus, the dichotomy between the widespread tissue expression of classical class I genes and the restricted tissue expression of class I genes of the Qa/Tla region may be due in part to differences in the cis acting regulatory sequences that interact with trans-acting nuclear factors to direct transcription.
Characterization of "regulatory" idiotope-specific T cell clones to a monoclonal anti-idiotypic antibody mimicking a tumor-associated antigen (TAA).
Authors: Saeki Y , Chen J J , Shi L F , Raychaudhuri S , Köhler H 
Published: December 2022

Abstract
As reported previously, 3A4 is a paratope-specific anti-idiotypic mAb and induces cellular and humoral anti-tumor-associated Ag (TAA) responses. In this study, the specificity, MHC restriction and Ag processing requirement of Th cell lines and clones were determined that recognize an idiotypic determinant (Id) on 3A4. The anti-Id-3A4 is part of a tumor-associated idiotypic network which is involved in the regulation of the immunity against the DBA/2 L1210/GZL tumor. These 3A4-Id-specific T cell clones are phenotypically Th cells and recognize Id in the context of MHC class II molecules under MHC restriction. Moreover, the recognition of Id by these T cell clones is chloroquine sensitive, suggesting that they recognize processed Id. However, the 3A4-Id-specific T cell clones respond only to 3A4 and not to TAA. Because these clones do not recognize TAA, their biologic role in antitumor immunity could be as regulatory T cells involved in the idiotypic network regulation.
Induction of tumor-specific in vivo protective immunity by immunization with tumor antigen-pulsed antigen-presenting cells.
Authors: Shimizu J , Suda T , Yoshioka T , Kosugi A , Fujiwara H , Hamaoka T 
Published: December 2022

Abstract
The present study investigates the role of APC in inducing tumor-specific in vivo protective immunity. Thy-1+ cell-depleted, Mac-1+ cell-enriched fraction of normal BALB/c spleen cells were used as a source of APC. These APC were cultured in vitro with the membrane fraction isolated from CSA1M fibrosarcoma derived from BALB/c strain. The administration of such APC into naive BALB/c mice generated the capacity of these animals to reject the subsequently challenged viable CSA1M tumor cells. Although the induction of anti-CSA1M in vivo protective immunity required three consecutive immunizations with more than 10(5) APC which had been pulsed in vitro with 200 to 300 micrograms protein of CSA1M membrane fraction, the immunity was induced irrespective of whether APC were administered via s.c., i.v., or i.p. route. This immunity was tumor-specific, inasmuch as the inoculation of CSA1M or Meth A fibrosarcoma membrane component-pulsed APC resulted in the selective immunity against the challenge with homologous types of tumor cells. The CSA1M-specific in vivo protective immunity was also induced by injecting APC pulsed with solubilized CSA1M membrane components. Moreover, it was demonstrated that the efficiency for inducing anti-CSA1M immunity was much higher in the utilization of tumor Ag-pulsed APC than in the immunization with tumor Ag emulsified in CFA. These results indicate the critical role of APC in generating tumor rejection immunity in vivo and this model presents a novel approach to induce tumor-specific immunity without using tumor cells themselves.
The intracellular precursor of IL-1 beta is associated with microtubules in activated U937 cells.
Authors: Baldari C T , Telford J L 
Published: December 2022

Abstract
Treatment of the human histiocytic leukemia cell line U937 with PMA and LPS results in the induction of expression of IL-1. Rabbit polyclonal antibodies raised against mature rIL-1 have been used to investigate the intracellular location of the IL-1 beta precursor in U937 cells. The pattern of indirect immunofluorescence staining seen with these antibodies overlaps substantially with that seen by using a mAb raised against beta-tubulin. Depolymerization of tubulin by incubation of the cells at 0 degrees C before fixation results in the disruption of the pattern of IL-1 staining. IL-1 beta precursor in extracts of activated U937 cells is shown to co-cycle with exogenously added tubulin through two rounds of in vitro depolymerization/polymerization. In addition, immunoprecipitation of IL-1 from cell extracts at 30 degrees C but not at 0 degrees C results in co-precipitation of tubulin. Thus the IL-1 beta precursor is shown in vivo and in vitro to associate with the microtubules of the cytoskeleton.
IL-6 modulates the synthesis of a specific set of acute phase plasma proteins in vivo.
Authors: Marinkovic S , Jahreis G P , Wong G G , Baumann H 
Published: December 2022

Abstract
Human rIL-6, produced either in COS cells or Escherichia coli, similarly stimulates the production of acute phase plasma proteins in cultured human and rat hepatoma cells. This anabolic effect in hepatoma cells suggested a potential in vivo role of the cytokine in mediating the hepatic response to inflammation. Injection of IL-6 into adult male rats elicited a cytokine-specific change in the liver expression of acute phase proteins. As predicted from in vitro studies, glucocorticoids were needed to achieve a maximal IL-6 response in vivo. Optimal conditions were found to be two i.p. injections of 35 to 120 micrograms IL-6 and 65 micrograms dexamethasone per kg body weight administered at 12-h intervals. Within 24 h, the plasma concentrations for alpha 2-macroglobulin, fibrinogen, thiostatin, and hemopexin were increased to levels approximating those observed in acute phase animals. These results support the notion that direct interaction of IL-6 with the liver is an essential part in initiating the hepatic acute phase reaction.
Prostaglandin E2-dependent induction of granulocyte-macrophage colony-stimulating factor secretion by cloned murine helper T cells.
Authors: Quill H , Gaur A , Phipps R P 
Published: December 2022

Abstract
PG are known to inhibit T cell proliferation, at least in part by suppressing IL-2 production, but effects of PG on the production of other lymphokines have not been well studied. We have found that PGE2 and PGE1, but not PGF2 alpha, inhibit both proliferation and production of granulocyte-macrophage (GM)-CSF by murine TH clones stimulated with Ag or anti-CD3 antibody. Thus, signals generated via the Ag receptor:CD3 complex were inhibited by PGE. Most interesting, however, was the finding that PGE2 and PGE1 could act synergistically with IL-2 for the induction of GM-CSF in some TH1 clones. Dependence on PGE2 for this response was not found in all clones, as some TH1 cells could produce GM-CSF after IL-2 alone, and some cells did not produce GM-CSF even in the presence of PGE2 and IL-2. These observations indicate that there is a subset of TH1 cells receptive to a stimulating activity of PGE2 in the presence of IL-2. PGE2 is known to elevate cAMP levels in T cells. Therefore, we tested whether other agents known to increase cAMP, such as forskolin and cholera toxin, could act in conjunction with IL-2 to induce GM-CSF secretion. As was found with PGE2, these compounds also induced GM-CSF activity in the presence of IL-2, suggesting a critical role for cAMP in this process. Overall these data indicate that the requirements for activation of GM-CSF secretion vary among individual T cells. Most importantly they provide the first evidence that E-series PG are positive signals for lymphokine induction in certain T cells, whereas simultaneously acting as negative signals limiting proliferation. This result also suggests that treatment with anti-inflammatory drugs that decrease PGE2 concentrations may inhibit lymphokine secretion normally stimulated by this pathway.
Human B cell proliferation in response to IL-4 is associated with enhanced production of B cell-derived growth factors.
Authors: Tadmori W , Lee H K , Clark S C , Choi Y S 
Published: December 2022

Abstract
To investigate the capacity of human IL-4 to function as a B cell growth factor (BCGF), we studied its ability to promote proliferation of a selected B cell line. We show that the cell line, designated A4, proliferated in response to IL-4 in a dose-dependent manner. The A4 cells also proliferated in response to their own B cell derived growth factor (B. BCGF), suggesting autocrine-mediated growth. The ability of IL-4 to induce proliferation of the A4 cell line was dependent on the level of autocrine growth. At low cell density, IL-4 induced marked dose-dependent proliferation. However, as A4 cell density increased, the ability of IL-4 to induce proliferation was diminished. The possibility that IL-4 may be mediating the autocrine growth of A4 cells was ruled out, because A4 cell-derived BCGF failed to induce CD23/low affinity receptors for the Fc region of IgE on activated tonsillar B cells and anti-IL-4 antibody did not block B. BCGF activity. We found that IL-4 stimulation of A4 cells and activated tonsillar B cells is associated with enhanced production of B. BCGF. These data indicate that human IL-4 has the capacity to promote proliferation of the B cell line A4, and that the ability of IL-4 to function as BCGF is associated with enhanced autocrine growth of activated B cells.