bluuebunny/crossref_metadata_2025_split huggingface dataset:
NF-X2 that binds to the DRA X2-box is activator protein 1. Expression cloning of c-Jun.
Authors: Andersson G , Peterlin B M 
Published: January 2023

Abstract
Human class II MHC Ag are a family of cell surface glycoproteins. Their constitutive expression is limited to B lymphocytes and thymic epithelial cells. In many other cells their expression can be induced by IFN-gamma. Conserved upstream promoter sequences regulate this tissue-specific expression of class II genes. In the DRA promoter, one of these cis-acting regulatory motifs is the X2-box to which nuclear factor X2 (NF-X2) binds. Here, we present the isolation and characterization of the full-length cDNA clone encoding NF-X2. This cDNA clone was isolated by expression cDNA cloning, and encodes the human c-Jun protein, which together with c-Fos forms the heterodimeric activator protein-1 transcription complex. Whereas c-Fos/c-Jun heterodimers do not exist in B cells, they form and bind to the X2-box in class II nonexpressing cells. Thus, c-Fos/c-Jun heterodimers might contribute to the repression of DRA gene expression.
Induction of germ-line and mature C epsilon transcripts in human B cells stimulated with rIL-4 and EBV.
Authors: Jabara H H , Schneider L C , Shapira S K , Alfieri C , Moody C T , Kieff E , Geha R S , Vercelli D 
Published: January 2023

Abstract
EBV and rIL-4 induce T cell-independent IgE production by normal human B cells. We demonstrate here that EBV and IL-4 induced the synthesis of IgE by surface IgE-negative B cell precursors isolated by cell sorting. This result suggests that the induction of IgE by EBV and IL-4 results not merely from the expansion of a precommitted surface IgE-positive B cell population but more likely from IL-4-directed switching to IgE. At the molecular level, IL-4 and EBV induced the appearance of 2.0- and of 1.8-kilobase (kb) RNA bands, both of which hybridized with an 0.88-kb HinfI fragment spanning part of the C epsilon 1 exon and the entire C epsilon 2 exon. The 1.8-kb band but not the 2.0-kb band also hybridized with a cloned genomic 0.7-kb SmaI fragment located approximately 2 kb upstream of C epsilon. Thus, EBV and IL-4 induced germline (1.8-kb) as well as mature (2.0-kb) C epsilon transcripts. IL-4 by itself induced germ-line C epsilon transcripts but not mature C epsilon transcripts in purified normal B cells. IL-4 failed to induce IgE synthesis in established EBV B cell lines and failed to induce 2.0-kb mature C epsilon transcripts but induced 1.8-kb germ-line C epsilon transcripts. These data show that IL-4 is sufficient for the induction of C epsilon germ-line transcription. In contrast, the transcription of mature epsilon mRNA requires an additional activating signal, provided by infection with EBV. Established EBV transformation results in a dissociation between germ-line C epsilon transcription and the ability to undergo IgE switching in response to IL-4.
In vivo immune selection of a Moloney murine leukemia virus-induced tumor results in the loss of viral- but not tumor-associated antigens.
Authors: Jiang D , Flyer D C 
Published: January 2023

Abstract
A protocol of in vivo immune selection has been used to isolate a variant of the Moloney murine leukemia virus (MuLV)-induced tumor MBL-2. Characterization of the tumor variant indicated that selection resulted in the isolation of a cell which is incapable of producing infectious virus and no longer capable of synthesizing viral proteins. Although the failure to express viral Ag has rendered the variant tumor cells resistant to lysis by CTL specific for MuLV viral Ag, the variant tumor cells retained their susceptibility to lysis by CTL which appear to be directed against an MuLV-induced tumor-associated Ag. The data indicate that the expression of nonviral tumor-associated Ag by MBL-2 is not dependent upon continued viral gene expression.
Blocking of mixed lymphocyte reaction by spleen cells from total lymphoid-irradiated mice involves interruption of the IL-2 pathway.
Authors: Field E H , Becker G C 
Published: January 2023

Abstract
Treatment with total lymphoid irradiation (TLI) before organ transplantation results in high incidences of donor-specific tolerance. However, the exact mechanism of how TLI induces or maintains tolerance is not known. In many experimental systems of tolerance, lack of IL-2 plays a central role in tolerance induction, as stimulation of immunocompetent cells with Ag in an insufficient IL-2 environment results in tolerance. To examine whether tolerance induction by TLI might involve the IL-2 pathway, we examined how TLI cells affect the ability of immunocompetent cells to produce IL-2 and express IL-2R in the MLR. Responder cells from MLR cultures in which cells from TLI-treated mice were added proliferated 50 to 70% less and produced 68 to 94% less IL-2 bioactivity than responder cells from control cultures. However, coculture of TLI cells into MLR did not alter IL-2R expression on responder cells, as measured by two-color FACS analysis. We found no evidence that TLI cells deleted MLR responder cells. Interestingly, exogenous IL-2 did not restore proliferation of MLR responder cells. These results suggest that TLI may induce tolerance by interrupting the IL-2 pathway in immunocompetent cells. Moreover, that exogenous IL-2 failed to restore immunocompetence suggests that tolerance in the TLI model may be easy to induce and very stable, and provides a rationale for the higher incidences of donor-specific tolerance after TLI treatment.
Anti-IgM antibody-induced cell death in a human B lymphoma cell line, B104, represents a novel programmed cell death.
Authors: Ishigami T , Kim K M , Horiguchi Y , Higaki Y , Hata D , Heike T , Katamura K , Mayumi M , Mikawa H 
Published: January 2023

Abstract
We investigated the mechanisms of anti-IgM antibody-induced cell death in a recently established human surface IgM+ IgD+ B lymphoma cell line, B104, the growth of which is irreversibly inhibited by anti-IgM antibody but not by anti-IgD antibody, and compared it with the cell death of T cells via TCR/CD3 complex and with the cell death of a murine anti-IgM antibody-sensitive B lymphoma cell line, WEHI-231. The rapid time course of B104 cell death and its requirements for de novo macromolecular synthesis and Ca2+ influx suggest that anti-IgM antibody-induced B104 cell death is an active Ca(2+)-dependent programmed cell death. Moreover, cyclosporin A rescued B104 cells from this lethal signal, via surface IgM, suggesting that the intracellular mechanisms involved are quite similar to those of T cell death. DNA fragmentation, which has been reported in TCR/CD3 complex-mediated T cell death, apoptosis, was not involved in the B104 cell death process, but the possible involvement of DNA single-strand breaks was suggested. Observations under light microscopy and transmission electron microscopy indicated that the morphologic features of dying B104 cells resembled necrosis rather than apoptosis. B104 cell death was shown to be quite distinct from that of WEHI-231 in cell death kinetics, the mode of cell death, and the response to cyclosporin A. These data collectively indicate that the death of B104 cells resulting from surface IgM cross-linking represents a hitherto undefined mode of programmed cell death.
CD31, a novel cell surface marker for CD4 cells of suppressor lineage, unaltered by state of activation.
Authors: Torimoto Y , Rothstein D M , Dang N H , Schlossman S F , Morimoto C 
Published: January 2023

Abstract
In this study, we examined the role of CD31 as a cell surface marker for subsets of human CD4 cells. CD31, as defined by a newly developed mAb termed anti-1F11, can divide activated as well as resting CD4 cells into distinct functional subpopulations, based on its surface expression. Among CD4 cells freshly isolated from peripheral blood, anti-1F11 preferentially reacts with the CD45RA+ subset. The majority of helper activity for B cell IgG synthesis and memory function to recall Ag such as tetanus toxoid or mumps was found within the CD31- CD4 cell population, whereas CD31+ CD4 cells provided poor helper function for B cell IgG synthesis and were more responsive to Con A and autologous MHC (autologous MLR). The expression of CD31 on CD45RA+ CD4 cells did not change after activation, despite the loss of CD45RA from the cell surface. Conversely, CD31 was not acquired after activation of CD45RO+ CD45RA- CD4 cells. Furthermore, activated CD4 cells expressing CD31 can induce suppressor function for B cell IgG synthesis, whereas the reciprocal population of activated CD4 cells (CD31-) provide strong helper function for B cell IgG production. Finally, IL-4 production could only be induced by stimulation with PMA and ionomycin in either resting or activated CD31- CD4 cells. Thus, CD31 may prove useful in defining CD4 populations with reciprocal functional programs. Moreover, unlike other markers used for this purpose, the expression of CD31 does not change after activation and may serve as a more useful marker for identification of cells of suppressor or helper lineage.
Antigen-specific CD8+ T cells switch the immune response induced by antigen from an IgG to a cell-mediated mode.
Authors: Tuttosi S , Bretscher P A 
Published: January 2023

Abstract
We have developed an in vivo/in vitro immunization procedure with xenogeneic RBC as Ag that results in the generation of a lymphoid population that expresses potent delayed-type hypersensitivity (DTH) and produces little, if any, antibody. This lymphoid population contains Ag-specific CD8+ T cells that can inhibit the induction of a strong IgG response. These CD8+ T cells are shown to not only inhibit the antibody response in an Ag-specific manner but allow the Ag to induce cells of the target population to express DTH. Furthermore, the Ag-specific inhibition of the antibody response and the Ag-specific enhancement of the induction of DTH appear to be coordinately regulated, as the same number of CD8+ T cells cells is required to achieve both effects. Thus these CD8+ T cells are shown to switch the response induced by Ag from a humoral to a cell-mediated mode. These regulatory characteristics are consistent with a physiologic role for these cells of ensuring the absence of antibody production during a strong, cell-mediated response.
Generation of nondividing high rate Ig-secreting plasma cells in cultures of human B cells stimulated with anti-CD3-activated T cells.
Authors: Vernino L , McAnally L M , Ramberg J , Lipsky P E 
Published: January 2023

Abstract
The capacity of human B cells to differentiate into high rate nondividing antibody-secreting plasma cells was investigated. Highly purified human peripheral blood B cells were stimulated with polyclonal B cell activators in the presence of a variety of recombinant cytokines (IL-2, IL-4, IL-6). Maximal production of Ig of all isotypes was observed when B cells were stimulated with intact T cells that were activated with mAb to the CD3 molecular complex. In these cultures, Ig production continued for more than 16 days. Moreover, differentiation to nondividing high rate Ig-producing cells was induced, as evidenced by a ninefold increase in the amount of Ig produced per Ig-secreting cell and the acquisition of resistance of ongoing Ig secretion to the inhibitor of DNA synthesis, hydroxyurea. To determine whether intact T cells were required for the entire culture period to achieve maximal Ig production, B cells were cultured with activated T cells for various lengths of time, reisolated and cultured with fresh activated T cells or various cytokines, then analyzed for Ig secretion. B cells preactivated for 6 days with anti-CD3-stimulated T cells required contact with intact T cells for continued Ig secretion. However, after 9 days of preactivation, dividing B cells responded maximally to anti-CD3-stimulated T cells, whereas cytokines were able to drive continued IgG secretion by nondividing B cells in the absence of intact T cells. IL-6 alone, or in combination with either IL-2 or IL-4, was the major cytokine driving ongoing Ig secreting by nondividing preactivated B cells. These results suggest that continued clonal expansion of Ig-secreting B cell blasts requires intact anti-CD3-activated T cells, whereas terminal differentiation of B cells into plasma cells after extensive clonal expansion is driven by cytokines, most notably IL-6.
Inhibition of IgE binding to RBL-2H3 cells by a monoclonal antibody (BD6) to a surface protein other than the high affinity IgE receptor.
Authors: Hamawy M M , Oliver C , Siraganian R P 
Published: January 2023

Abstract
A mAb was isolated (mAb BD6) that recognized a surface glycoprotein on rat basophilic leukemia cells (RBL-2H3). The antibody bound to 2 x 10(6) molecules/cell and specifically blocked IgE binding (50% inhibition with 3.48 +/- 0.51 micrograms/ml; mean +/- SEM), although neither IgE nor anti-high affinity IgE receptor (anti-Fc epsilon RI) mAb blocked mAb BD6 binding to the cells. mAb BD6 did not affect the rate of dissociation of cell-bound IgE, nor did it induce or inhibit the internalization of IgE. mAb BD6 did not release histamine. However, it did cause rapid spreading of the cells. By 1 h the cells had retracted to a spherical shape with their surface covered with membranous spikes, and they could easily be detached from the tissue culture plate. These changes differed from those observed after Fc epsilon RI activation. mAb BD6 immunoprecipitated a complex of two proteins, 38 to 50 kDa and 135 kDa from 125I-surface labeled rat basophilic leukemia cells that are not subunits of Fc epsilon RI. Chemical cross-linking studies showed that these molecules are associated on the cell surface. By immunoblotting, mAb BD6 reacted with a 40-kDa protein. Therefore, mAb BD6 binds to a surface protein that is close to the Fc epsilon RI and sterically inhibits 125I-IgE binding.
Differing macrophage and lymphocyte roles in resistance to Legionella pneumophila infection.
Authors: Yamamoto Y , Klein T W , Newton C , Friedman H 
Published: January 2023

Abstract
Similar to guinea pig macrophages and human monocytes, macrophages from the peritoneal cavity of thioglycolate pretreated A/J mice are permissive for growth of Legionella pneumophila. In contrast, macrophages from BDF1 mice are not permissive for L. pneumophila. Lymphocytes from A/J and BDF1 mice proliferated in response to Legionella Ag but guinea pig lymphocytes did not. Also, splenocyte cultures from A/J mice treated with either Con A or Legionella vaccine produced supernatants which induced A/J macrophages to restrict Legionella growth, but guinea pig splenocyte culture supernatants obtained after stimulation with L. pneumophila vaccine did not induce Legionella growth restriction activity by guinea pig macrophages. Murine rIFN-gamma but not rIFN-alpha markedly inhibited growth of Legionella in A/J mouse macrophages and monoclonal anti-IFN-gamma antibody neutralized the anti-Legionella activity of culture supernatants from A/J mouse splenocytes responding to Legionella Ag. From these data, IFN-gamma appears to be an important factor in anti-Legionella activity of Ag-activated mouse splenocyte culture supernatants. Cyclosporin A, when given to either A/J or BDF1 mice, reduced the proliferation responses of splenocytes to T cell mitogens and also decreased the IFN production of A/J spleen cells to Legionella Ag. In addition, drug treatment decreased the resistance of A/J mice to Legionella infection as shown by an increase in the number of viable bacteria in the liver. However, injection of drug treated mice with lymphokine-rich splenocyte culture supernatant reconstituted the resistance of these animals. These results suggest an important role for lymphocyte activation and lymphokine production in the resistance of A/J mice to Legionella infection. The greater resistance of BDF1 mice, however, may result from nonpermissive macrophages and responsive lymphocytes. In the case of guinea pigs, susceptibility to Legionella infections may result from both the permissive nature of the macrophages and the relatively unresponsive nature of the lymphocytes in these animals.
Cloning and expression of a cDNA encoding a non-classical MHC class I antigen (HLA-E) in eosinophils from hypereosinophilic patients.
Authors: Truong M J , Gruart V , Capron A , Capron M , Tourvieille B 
Published: January 2023

Abstract
A cDNA library, constructed from purified blood eosinophils, was screened with the B cell CD23 cDNA probe. A clone designated EO15 has been isolated and found to encode a non-classical HLA class I gene transcript. EO15 was compared with HLA-E and found to be 99.9% similar at the nucleotide level and to extend further in the 3' untranslated region. The presence of an additional polyadenylation signal in the EO15 3' end suggests that EO15 clone represents a copy of the 3.3-kb mRNA species detected in Northern blot analyses. HLA-E transcripts of 1.9 and 3.3 kb have been described in a variety of cell types. The two EO15 mRNA species, similar in size to the previously defined HLA-E mRNA, were present at high levels in blood leukocyte populations and at variable levels in different cell lines. The EO15 transcripts were found at abundant levels in hypodense and normodense eosinophils from hypereosinophilic patients. In situ hybridization confirmed the expression of EO15 mRNA in eosinophils. Neutrophils and lymphocytes from normal donors of from patients with hypereosinophilia also strongly expressed EO15 mRNA. Among the cell lines studied, the highest levels of EO15 transcripts were detected in B and monocytic cell lines, whereas intermediate and lower levels were found in eosinophilic, NK-like, megakaryocytic, and T cell lines, respectively. Similar to its effect on classical HLA class I transcripts, IFN-gamma increased the levels of EO15 mRNA in eosinophils and neutrophils from hypereosinophilic patients. These results suggest that purified blood eosinophils as well as neutrophils express EO15/HLA-E mRNA; however, further experiments are needed to investigate the localization and the function of EO15 protein products.
Allospecificities of B6D2F1 hybrid NK cell subsets defined by Ly-49A expression.
Authors: Basiri H , Kiura K , DeNardin E G , Nakamura I 
Published: January 2023

Abstract
More than 90% of IL-2-activated plastic-adherent murine splenocytes (A-LAK4 cells) are NK1.1+ NK cells and both H-2b/b homozygous C57BL/6- and H-2b/d heterozygous (C57BL/6 x DBA/2)F1 (B6D2F1)-derived populations of such cells contain an Ly-49A+ subset. In B6D2F1 A-LAK cells, as well as in freshly isolated spleen cells of the same mice, Ly-49A+ cells represent approximately 10% of NK1.1+ cells. However, the level of Ly-49A expression in B6D2F1 NK cells is lower than in C57BL/6 (B6). The cytolytic activity of B6- and B6D2F1-derived A-LAK cells against normal target cells is specific, and is in agreement with the known patterns of natural resistance in vivo against Hh-1-mismatched bone marrow allografts. H-2b lymphoma cells transfected with the Dd gene, but not the Ld gene, no longer express the Hh-1b phenotype that is recognized by B6D2F1 A-LAK cells, raising the possibility that this selective effect of the Dd gene on Hh-1b phenotype is related to the known inability of Ly-49A+ A-LAK cells to kill Dd-expressing tumor target cells. Depletion of Ly-49A+ A-LAK cells by Ab and complement reduces the lytic capacity of B6D2F1 A-LAK cells against normal B6 target cells of the Hh-1b phenotype to one-third of the original level. Conversely, positively selected Ly-49A+ A-LAK cells are enriched for the same activity. The results, therefore, favor the view that the Hh-1 phenotype of the target cells may be defined largely by the effector cell's recognition of class I Ags on the target cell surface.
Analysis of the requirements for class II-restricted T cell recognition of a single determinant reveals considerable diversity in the T cell response and degeneracy of peptide binding to I-Ed.
Authors: Fahrer A M , Geysen H M , White D O , Jackson D C , Brown L E 
Published: January 2023

Abstract
The amino acid sequences recognized by five I-E(d)-restricted and one E alpha A beta d-restricted murine T cell clones were determined. The clones had been raised to a synthetic peptide representing amino acids 305-328 of influenza virus hemagglutinin. It was found that although all of the T cell clones recognized a single 10-residue region of the peptide, 307KYVKQNTLKL316, different clones could recognize minimal ("core") determinants spanning 8, 9, or 10 of these amino acids. To see whether particular amino acids within the sequence 307-316 were universally important for T cell recognition, the six clones were assayed for their ability to tolerate single amino acid substitutions of the 10 residue peptide. In all, 190 analogues of the peptide in which each amino acid in the sequence was replaced, in turn, by each of the other 19 naturally occurring amino acids were tested. It was shown that 1) the six T cell clones had very different requirements for recognition of the peptide, 2) substitutions at every single position within the peptide could be shown to affect recognition in a T cell-specific manner, and 3) every single position within the peptide could be replaced by a large number of amino acids and still be recognized by at least one T cell clone. These results demonstrate the great diversity exhibited by the T cell repertoire in recognizing a 10-amino acid determinant, as well as the degeneracy of peptide binding to I-E(d).
NK cell subsets in the regulation of murine hematopoiesis. I. 5E6+ NK cells promote hematopoietic growth in H-2d strain mice.
Authors: Murphy W J , Raziuddin A , Mason L , Kumar V , Bennett M , Longo D L 
Published: January 2023

Abstract
NK cells are able to reject bone marrow allografts in lethally irradiated mice. 5E6 is a marker expressed on a subset of NK cells that is responsible for the rejection of H-2d homozygous bone marrow cell (BMC) allografts. This suggests that the 5E6+ NK cell subset somehow recognizes and is deleterious for H-2d BMC. However, unlike Ly-49+ NK cells, 5E6+ cells are not deleted or even down-regulated in H-2d-homozygous mice. We wanted to determine, therefore, the role of the 5E6+ and 5E6- NK cell subsets in the normal physiologic regulation of hematopoiesis in H-2d strains of mice. Surprisingly, both in vivo depletion studies of normal mice and studies in which the subsets were purified and cultured with syngeneic BMC in vitro demonstrated that in H-2d mice, the 5E6+ subset of NK cells did not inhibit, but instead promoted, growth of H-2d BMC. Depletion of the 5E6+ subset also resulted in decreased marrow engraftment after syngeneic bone marrow transplantation in H-2d mice. Analysis of the cell culture supernatants of the purified subsets indicated that the functional effects of the subsets on hematopoiesis correlated with the relative amounts of hematopoietic growth-promoting cytokines produced by the NK cells. These results demonstrate that physiologically relevant subsets of NK cells exist that are involved in the homeostatic regulation of hematopoiesis and that they can be distinguished on the basis of 5E6 expression.