bluuebunny/crossref_metadata_2025_split huggingface dataset:
V kappa gene usage, idiotype expression, and antigen binding among clones expressing the VHX24 gene family derived from naive and anti-idiotype immune BALB/c mice.
Authors: Bonilla F A , Zaghouani H , Rubin M , Bona C 
Published: December 2022

Abstract
The BALB/c myeloma protein ABPC48 binds beta(2-6)-linked fructosans and expresses genes derived from the VHX24 and V kappa 10 gene families. We have selected 30 hybridomas expressing the VHX24 gene family derived from mitogen-stimulated spleen cells of naive BALB/c mice and mice injected at birth with the syngeneic monoclonal anti-ABPC48Id, IDA10. The majority of mAb with kappa L chains uses V kappa 1. Antibodies reacting with IDA10 use both V kappa 10 and V kappa 1. Most of these VHX24+ mAb reacted with one or more members of a limited panel of predominantly polysaccharide Ag that have been previously observed to interact with antibodies expressing the VHX24 gene family. Nucleotide sequencing of selected VH and V kappa genes shows a very low frequency of somatic mutation. The effect of neonatal anti-Id injection on VHX24-V kappa pairing and Id expression is discussed.
Mapping of multiple B cell epitopes on the 70-kilodalton autoantigen of the U1 ribonucleoprotein complex.
Authors: Cram D S , Fisicaro N , Coppel R L , Whittingham S , Harrison L C 
Published: December 2022

Abstract
High titer IgG autoantibodies to the 70-kDa polypeptide component (p70) of the U1 ribonucleoprotein (RNP) complex occur in the sera of patients with mixed connective tissue disease, SLE, and related rheumatic diseases. To gain insight into the pathogenesis and diversity of this antibody response we have used recombinant DNA technology to map the linear B cell epitopes on p70. A full length 1.7-kb cDNA clone encoding p70 was isolated from a human placental library and restriction fragments or polymerase chain reaction-generated fragments of the gene subcloned into the bacterial expression vector pGEX. Purified fusion proteins representing specific regions of p70 were immunoblotted with a panel of 70 anti-(U1)RNP+ sera containing anti-p70 antibodies. Six epitopes, four major (A, B, C, and F) and two minor (D and E) were mapped and were located throughout the molecule. The anti-(U1)RNP sera displayed heterogeneity in their pattern of reactivity to the six epitopes although reactivity to epitope C was more frequently associated with SLE rather than mixed connective tissue disease. The identification of multiple B cell epitopes on p70 is consistent with the concept that this self Ag drives the autoantibody response.
Complement activation induced by human C-reactive protein in mildly acidic conditions.
Authors: Miyazawa K , Inoue K 
Published: December 2022

Abstract
Human C-reactive protein (CRP) is known to activate the C system upon reaction with phosphocholine-containing or polycation-containing ligands. We found that, even in the absence of these ligands, CRP caused C activation in mildly acidic conditions. The optimum pH for the activation was 6.3, which is within a physiologic range normally found at an inflammatory locus. In this activation, C components C1 and C4 were extensively consumed, C2 and C3 were moderately consumed, and C5 was only slightly consumed. These results indicate that the activation is mediated via the classical pathway, but is restricted to the early stage of the C cascade. As with the plasma contact system, the reaction proceeded in glass tubes but not in polypropylene tubes. However, even in polypropylene tubes, the reaction proceeded after the supplement of kaolin particles to the system. Probably the C activation induced by CRP at a mildly acidic pH required negatively charged surfaces. Analyses of circular dichroism and fluorescence spectra indicate that CRP undergoes a pH-dependent conformational change, thus affecting the reactivity of CRP with the C system.
IFN-gamma potentiates the accumulation of diacylglycerol in murine macrophages.
Authors: Sebaldt R J , Prpic V , Hollenbach P W , Adams D O , Uhing R J 
Published: December 2022

Abstract
Activation of mononuclear phagocytes for a variety of functional responses is potentiated by prior exposure to IFN-gamma. Inasmuch as protein kinase C has been suggested to mediate several of these responses, we have examined the effects of IFN-gamma exposure on subsequent accumulation of sn-1,2-diacylglycerol (DAG). Exposure of murine macrophages to IFN-gamma (greater than 4 h) results in an increase in basal DAG as well as potentiating DAG accumulation in response to the macrophage chemoattractant, platelet-activating factor (PAF). An increased DAG accumulation was similarly observed in response to PMA and ionomycin. Our results further indicate that the increased DAG accumulation during activation of macrophages is unlikely to involve alterations in phosphatidylinositol metabolism. PAF-stimulated production of [3H]inositol phosphates was not altered by the prior exposure of macrophages to IFN-gamma. Similarly, IFN-gamma did not potentiate the ability of PAF to cause an increase in cytosolic calcium. Our data indicate that phosphatidylcholine metabolism may be involved in IFN-gamma-regulated DAG accumulation. Exposure of [3H]choline-labeled macrophages to IFN-gamma resulted in an increase in the basal level of aqueous [3H]choline metabolites as well as potentiating the production of [3H]choline in response to PAF, PMA, and ionomycin. Our results thus suggest that the potentiated protein kinase C-mediated responses occurring during macrophage activation may be due to potentiated DAG accumulation independent of potentiated phosphatidylinositol metabolism.
Bacteria-infected fibroblasts have enhanced susceptibility to the cytotoxic action of tumor necrosis factor.
Authors: Klimpel G R , Shaban R , Niesel D W 
Published: December 2022

Abstract
The susceptibility of bacteria-infected fibroblasts to the cytotoxic action of tumor necrosis factor was investigated. L cells infected with Shigella flexneri, Salmonella typhimurium, or Listeria monocytogenes, had an enhanced susceptibility to the cytotoxic activity of TNF-alpha. This enhanced susceptibility was dependent upon the challenge dose of bacteria, the concentration of TNF, and upon the exposure time of bacteria-infected cells to TNF. L cells infected with S. flexneri were susceptible to the cytotoxic action of TNF at 2 to 6 h after bacterial infection. In contrast, L cells infected with S. typhimurium or L. monocytogenes did not show enhanced susceptibility to TNF until 14 h postbacterial infection and exposure to TNF. Enhanced susceptibility to TNF was dependent on bacterial invasion because fibroblasts pretreated with a noninvasive isogenic variant of S. flexneri, UV-treated invasive bacteria, bacterial cultural supernatant, or bacteria LPS were no more susceptible to TNF than untreated cells. Enhanced susceptibility to TNF by bacteria-infected cells was not unique to L cells. Mouse embryo fibroblasts and HeLa cells also showed similar reactivities after bacteria infection. Bacteria-infected cells were greatly suppressed in host cell protein synthesis that may play an important role in their enhanced susceptibility to TNF. These results suggest that an important role of TNF in host defense against bacterial infections is its cytotoxic activity against bacteria-infected cells.
Transcriptional control of c-myc gene expression during stimulation of murine B lymphocytes.
Authors: Buckler A J , Rothstein T L , Sonenshein G E 
Published: December 2022

Abstract
The binding of ligand to surface IgR results in the initial activation of B cells. As shown by experiments in which B cells are polyclonally stimulated with anti-Ig antibody, this includes an early increase in c-myc gene expression. In our study a correlation between increases in the rate of gene transcription and the level of c-myc mRNA was observed both with the brief increase in c-myc expression that is induced by anti-Ig, as well as with the more intense and prolonged expression of c-myc that follows treatment with anti-Ig plus the cytoskeleton perturbing agent, cytochalasin. Elevation of the rate of initiation was detected with both stimulatory regimens although the combination of anti-Ig plus cytochalasin increased the rate of elongation in addition to the rate of initiation. These results suggest that stimulation of B lymphocytes alters expression of trans-acting factors that regulate transcription of the c-myc gene.
Tumor idiotype vaccines. VII. Analysis and correlation of structural, idiotypic, and biologic properties of protective and nonprotective Ab2.
Authors: Raychaudhuri S , Kang C Y , Kaveri S V , Kieber-Emmons T , Köhler H 
Published: December 2022

Abstract
We have previously generated and used anti-Id mAb (Ab2) to induce protective immunity against the L1210 DBA/2 tumor and for immunotherapy of established tumors. Among various anti-Id that were typed serologically as internal image Ab2 of the mouse mammary tumor virus tumor-associated Ag gp52, only one induced protective immunity and was effective in immunotherapy. In this study we compared the structural, idiotypic, and network properties of the protective and nonprotective antiidiotypic antibodies. The DNA sequence of the variable regions of six anti-Id was determined. The VH sequence of four Ab2, including the protective Ab2, are highly homologous, whereas the VL sequences differ and were assigned to different Vk families. In addition, the DH sequence region of the same four Ab2 are identical, whereas one is highly homologous and another one without homology. Search for amino acid sequence homologies between the Ab2 and gp52 showed the strongest similarities in the CDR2 of the L chain from the protective Ab2. In addition, the CDR2 region also had homology with a T cell epitope on gp52. The biologic basis of effective idiotypic mimicry was studied at the level of Ab3 induced by the Ab2. Id inhibition analysis using Ab3 induced by either protective or nonprotective Ab2, revealed differences. Thus, there is evidence for differences among the Ab1-Ab2-Ab3 cascade induced by protective and nonprotective anti-Id.
Molecular characterization of anti-idiotype antibody-resistant variants of a murine B cell lymphoma.
Authors: Roth M S , Weiner G J , Allen E A , Terry V H , Harnden C E , Boehnke M , Kaminski M S , Ginsburg D 
Published: December 2022

Abstract
We have previously identified Id- tumor vaiants that emerge after anti-Id mAb therapy of the murine B cell lymphoma 38C13. This report characterizes the molecular basis for these variants. By using a modification of the polymerase chain reaction (PCR), mu and kappa Ig loci were sequenced from nine Id- variants derived directly by anti-Id immunoselection in vivo. Ig kappa loci sequence analysis was also performed from 10 additional variants amplified directly from tumor cells in vitro without immunoselection. We demonstrate that the molecular mechanism underlying tumor cell escape in this model is the spontaneous emergence of variants that have undergone kappa L chain gene "re-rearrangement" before positive selection by the anti-Id antibody. A second round of re-rearrangement was also demonstrated to occur within primary tumor variants. Re-rearrangement of the 38C13 tumor cell Ig kappa locus is strongly biased toward use of variable kappa genes within the conserved V kappa-Ox1 gene family, although their use is not exclusive. With the use of RNA PCR re-rearrangement was documented to occur in vitro at a frequency of approximately 1.0 x 10(-5)/cell. These findings may have important implications for the application of anti-Id antibodies as a therapeutic approach for human lymphomas and for understanding of the Ig gene rearrangement process.
Expression of cross-reactive, shared idiotypes on anti-SEA antibodies from humans and mice with schistosomiasis.
Authors: Montesano M A , Freeman G L , Gazzinelli G , Colley D G 
Published: December 2022

Abstract
Immunoaffinity-purified antibodies against Schistosoma mansoni soluble egg Ag (SEA) from infected patients' sera differ idiotypically according to the donor's clinical form of the disease. The Id differ both by their ability to stimulate proliferation of anti-Id T cells and their recognition by anti-Id-specific sera. Also, mice infected with S. mansoni develop anti-Id T and B cell responses against mouse anti-SEA antibodies. We now show that anti-SEA antibodies from serum pools of chronic, but asymptomatic patients (AM1 and AM5) stimulate proliferation of spleen cells from mice infected with S. mansoni. However, AM8, anti-SEA antibodies from hepatosplenic patients, did not stimulate these spleen cells. The murine responses directly parallel patient studies where AM1 and AM5 Id-stimulated human PBMC, but AM8 Id did not. In competitive ELISA, using AM1 or AM-5-specific rabbit antisera or human anti-SEA mAb E5-specific rabbit antiserum, sera from mice infected for 8 and 16 wk (but not from uninfected mice) compete with AM1, AM5, or E5. These sera do not compete in the AM8/anti-AM8 competitive ELISA. Sera from 8-wk-infected mice inhibit more against AM1, AM5, and E5 than do sera from later infections, and anti-SEA immunoaffinity-purified antibodies from 8-wk-infected mice stimulate spleen cells from infected mice more than anti-SEA antibodies from sera of mice late in infection. However, spleen cells from more chronically infected mice are more responsive to either the murine or human anti-SEA antibody preparations than cells from mice with earlier infections. Both the ELISA data and lymphocyte responses indicate that anti-SEA antibodies from mice infected with S. mansoni for 8 wk bear Id cross-reactive with those expressed on anti-SEA antibodies from humans with chronic, asymptomatic schistosomiasis, but not those from hepatosplenic patients.
A distinct population of nonphagocytic and low level CD4+ null lymphocytes produce IFN-alpha after stimulation by herpes simplex virus-infected cells.
Authors: Sandberg K , Matsson P , Alm G V 
Published: December 2022

Abstract
Human PBMC were stimulated for 6 h in vitro by HSV or Sendai virus (SV) and analyzed by flow cytometry. IFN-alpha producing cells (IPC) were identified through their content of IFN-alpha mRNA by in situ hybridization using a 35S-labeled IFN-alpha 2 cRNA probe. The IPC induced by HSV-infected WISH cells lacked capacity to adhere to and phagocytose latex particles. The induction of IFN-alpha by free infectious SV occurring in monocytes was abolished by phagocytosis of latex particles present in the cultures during the induction period. Such latex particles actually enhanced the IFN-alpha response induced by glutaraldehyde-fixed HSV- or SV-infected WISH cells or by free intact HSV. The HSV-induced IPC did not express the CD14 Ag expressed on monocytes. Cell sorting was performed on HSV-induced PBMC labeled with phycoerythrin-conjugated anti-CD3 and FITC-conjugated anti-CD4 mAb. A small population consisting of 1.4% of all PBMC, which was CD3- but expressed low but significant levels of CD4, contained the majority of the IPC with a 50-fold increase of their frequency. This cell population had a forward- and right-angle light scatter different from typical monocytes/macrophages. The results therefore further delineate IPC among PBMC into monocytes, being stimulated by viruses such as SV. Another distinct population of infrequent but highly efficient IPC, tentatively designated natural IFN-alpha producing cells, is activated by stimuli such as HSV.
Generation of class I MHC-restricted T-T hybridomas.
Authors: Rock K L , Rothstein L , Gamble S 
Published: December 2022

Abstract
In this report we describe a system for the generation of functional, class I MHC-restricted, T-T hybridomas. The BW5147 cell line was transfected with the CD8 gene. BW5147 transfectants were obtained that stably expressed CD8 and this expression was maintained after somatic cell hybridization with activated T lymphocytes. To determine whether the stable expression of CD8 would facilitate the generation of class I MHC-specific T-T hybridomas, the transfected cells were fused with alloreactive T cells and the resultant hybrids were screened for their ability to produce lymphokines in response to antigenic stimulation. Somatic cell hybridizations with BW5147-CD8 transfectants give rise to a much higher frequency of class I MHC-specific T-T hybridomas relative to parallel fusions with BW5147. To determine whether the BW5147-CD8 transfectants would also support the generation of Ag-specific, class I MHC-restricted T-T hybridomas, they were fused with OVA-specific CTL. Several T-T hybrid clones were identified that produced lymphokines after stimulation with a transfected APC that was synthesizing OVA, or with a tryptic digest of OVA in the presence of syngeneic APC. The stimulation by Ag was MHC-restricted and mapped to the Kb molecule. An anti-CD8 mAb inhibited the stimulation of these hybridomas by Ag plus APC, whereas their stimulation by mitogen was unaffected. Cytolytic activity was not detected when several of the OVA-specific or alloreactive hybridomas were tested for their ability to kill target cells bearing the appropriate Ag. These results demonstrate that the BW5147-CD8 transfectants allow the generation of class I MHC-restricted T-T hybridomas. The potential utility of this system is discussed.
MHC class II-restricted presentation of native protein antigen by B cells is inhibitable by cycloheximide and brefeldin A.
Authors: St-Pierre Y , Watts T H 
Published: December 2022

Abstract
The presentation of protein Ag with MHC class II proteins involves the uptake of the protein Ag by endocytosis followed by processing, probably proteolysis, in an intracellular acidic compartment. However, there remains considerable controversy as to the precise route taken by the antigen and the MHC class II protein during this process. The unusual stability of Ag-MHC class II protein complexes has led to speculation that antigen can only associate with newly synthesized MHC class II molecules. An alternate possibility is that the MHC class II binding site can be regenerated within the cell during internalization and recycling of MHC class II proteins. To address these possibilities, three different murine B lymphoma lines were tested for their ability to process and present native protein Ag in the presence of the protein synthesis inhibitor cycloheximide or the protein synthesis inhibitor cycloheximide or the protein export inhibitor, Brefeldin A. Both agents blocked the presentation of native OVA or native hen egg lysozyme to Ag-specific T cell hybridomas. No effect was seen on peptide presentation or on presentation to allo- or autoreactive T cells. Inasmuch as Brefeldin A has been previously shown to block protein export without affecting protein internalization or protein degradation in the endocytic pathway, the simplest interpretation of these data is that antigenic fragments generated in the APC after uptake by the endocytic pathway, preferentially associate with newly synthesized rather than mature MHC class II proteins.
IL-2. A cofactor for induction of activated macrophage resistance to infection.
Authors: Belosevic M , Finbloom D S , Meltzer M S , Nacy C A 
Published: December 2022

Abstract
Macrophages cultured with IL-2 and IFN-gamma before exposure to microorganisms developed the ability to resist infection with the obligate intracellular parasite, Leishmania major. The induction of this macrophage effector response was maximal by 6 to 8 h after lymphokine addition, and was independent of lymphokine treatment sequence. Activation of macrophages for resistance to infection was the result of the direct action of IL-2 and IFN-gamma on macrophages: the effector reaction was demonstrated in both resident peritoneal macrophages depleted of T cells and bone marrow-derived cells, a homogeneous macrophage population. Radiolabeled murine rIFN-gamma, human rIL-2, and mAb to the IL-2R (7D4), each bound to murine bone marrow-derived macrophages in a specific and saturable manner, which suggested that unstimulated macrophages have receptors for both lymphokines. Treatment of macrophages with IFN-gamma increased the specific binding of IL-2; treatment of cells with IL-2, however, did not up-regulate the IFN-gamma-R. Addition of protein or RNA synthesis inhibitors (cycloheximide, emetine, actinomycin D) during exposure to rIL-2 and rIFN-gamma totally abrogated the ability of macrophages to express this effector reaction; inhibitors of protein kinase C, PG, or calcium redistribution had no effect. Soluble polyclonal anti-TNF-alpha antibodies in culture fluids after activation of macrophages with IL-2 and IFN-gamma totally abrogated the expression of resistance to infection. The T cell growth hormone IL-2 acts as cofactor with IFN-gamma for induction of a macrophage antimicrobial activity, and TNF-alpha may be the effector molecule for resistance to infection regulated by these two lymphokines.
Induction and regulation of IL-4 receptor expression on murine macrophage cell lines and bone marrow-derived macrophages by IFN-gamma.
Authors: Feldman G M , Finbloom D S 
Published: December 2022

Abstract
IL-4 is a T cell-derived cytokine that regulates the induction of proliferation of resting B cells, and appears to act on various other cells involved in the immune response. The pluripotential effects of IL-4 are dependent on the interaction of IL-4 with its receptor (IL-4R). Although the regulation and metabolism of these receptors have been examined on B and T cells, little is known about the metabolism or regulation of the IL-4R on macrophages. In studying the dynamics of IL-4R expression on the murine macrophage-like cell line J774.16, we detected the presence of low numbers of high affinity IL-4R (234 +/- 38, Kd = 110 +/- 11 pM) on the surface membrane. However, upon exposure to IFN-gamma, a potent macrophage activating cytokine, there was a rapid upregulation (within 45 min) of IL-4R (2750 +/- 178) on the cell surface, with no change in receptor affinity (Kd = 205 +/- 37 pM). Maximum expression occurred at 2 to 4 h with no further increase in IL-4R expression over the next 48 h. Cells pulsed with IFN-gamma for 45 min displayed maximum IL-4R expression by 4 h. The induction of IL-4R by IFN-gamma was dose dependent: as little as 0.5 ng/ml of IFN-gamma was capable of inducing IL-4R expression, with optimal induction at 10 ng/ml. The addition of the metabolic inhibitors actinomycin D and cycloheximide before the addition of IFN-gamma indicated that both RNA transcription and protein translation were required for this upregulation to occur.