bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pattern of joining (JH) gene usage in the human IgH chain is established predominantly at the B precursor cell stage.
Authors: Wasserman R , Ito Y , Galili N , Yamada M , Reichard B A , Shane S , Lange B , Rovera G 
Published: January 2023

Abstract
Preferential utilization of JH and D genes has been demonstrated in the rearranged IgH chain in human peripheral B cells. We report here that the same hierarchy of JH gene usage is observed in leukemic cells arrested in the B precursor stage of differentiation. Specifically, JH4 and JH6 accounted for 42.9% and 35.7%, respectively, of the JH gene usage in the leukemias compared with an expected frequency of 16.7% assuming unbiased gene usage. Within the D gene families, the DN1 gene appears to be overutilized in both populations, representing about 15% of the total gene usage compared with an expected frequency of 3.2%. Because 21 of the 36 leukemias contained only nonproductive IgH rearrangements, the preferential gene usage could not have arisen from pre-B cells that have undergone clonal selection after a productive rearrangement but before surface Ig expression. Nonproductive rearrangements exhibited the biased gene usage seen for productive rearrangements. These findings suggest that a recombination bias favoring certain segments may be the actual mechanism responsible for the apparent preferential utilization of JH and D genes.
Insulin-like growth factor-I inhibits apoptosis in IL-3-dependent hemopoietic cells.
Authors: Rodriguez-Tarduchy G , Collins M K , García I , López-Rivas A 
Published: January 2023

Abstract
The death of hemopoietic cells on withdrawal of CSF occurs by a mechanism known as apoptosis characterized by the early degradation of chromatin into oligonucleosome-length fragments. Insulin-like growth factor I plays a pivotal role in the regulation of somatic cell growth as a mediator of growth hormone action. Animals with low levels of circulating IGF-I are more vulnerable to infections and have diminished immune responses. To analyze the possibility of a regulatory role of IGF-I on hemopoiesis and determine its mechanism of action, we have studied the effect of this growth factor on the survival and proliferation of two IL-3-dependent hemopoietic cell lines and in IL-3-responsive primary cultures of bone marrow-derived mast cells. In IL-3-depleted cultures, IGF-I prevented DNA fragmentation and apoptotic cell death. Insulin at high concentration had a weak protective action and IGF-II was inactive in suppressing apoptosis in these IL-3-dependent hemopoietic cells. Cell proliferation was also stimulated by IGF-I in the absence of other hemopoietic growth factors although it was a weak mitogen when compared with IL-3. These results indicate that circulating or locally produced IGF-I may promote survival of both the steady state hemopoietic precursor population and cytokine-producing cells and could therefore regulate hemopoiesis acting in a concerted manner with other CSF.
Involvement of beta 2-integrins in the migration of human natural killer cells.
Authors: Somersalo K , Tarkkanen J , Patarroyo M , Saksela E 
Published: January 2023

Abstract
Human large granular lymphocytes with the NK cell phenotype (CD16+ or CD56+CD3-) were greatly enriched among the cells which migrated spontaneously through untreated or albumin-coated, 3-microns pore size polycarbonate filters for 1 to 8 h. Three days of rIL-2 treatment (300 IU/ml) and 3 to 5 wk of rIL-2 treatment (100 IU/ml) generated a 2.7 +/- 0.9-fold and 5.6 +/- 0.8-fold increase in cell migration, respectively. The adhesion and subsequent migration of freshly isolated NK cells was mainly mediated by CD11b/CD18, because migration could be inhibited by 80 +/- 8% anti-CD11b (Mac-1) antibodies but not with antibodies against CD11a (LFA-1) or CD11c (p150,95), the other alpha-chains of the beta 2-integrins. After rIL-2 activation, however, CD11a/CD18 was the major receptor utilized in migration, inasmuch as anti-CD11a antibody caused a 69 +/- 8% reduction in the number of migrated cells. Anti-CD11b antibody decreased migration by 43 +/- 12%, and together these antibodies inhibited migration by 82 +/- 7%. Anti-CD11a alone did not have any effect on adhesion, but CD11a/CD18 cooperated in the adhesion because anti-CD11b decreased adhesion by 40 +/- 11% and together these antibodies inhibited adhesion by 74 +/- 6%. The ability of large granular lymphocytes to rapidly utilize beta 2-integrins and unidentified ubiquitous ligands for binding and migration may be significant for their capacity to function in the first line of immune defense under highly variable conditions.
Adherence of rat basophilic leukemia (RBL-2H3) cells to fibronectin-coated surfaces enhances secretion.
Authors: Hamawy M M , Oliver C , Mergenhagen S E , Siraganian R P 
Published: January 2023

Abstract
Rat basophilic leukemia (RBL-2H3) cells are a useful in vitro model for studies of mast cells and basophils. We examined the adherence of RBL-2H3 cells to different extracellular matrix proteins and the effect of such attachment on secretion. The cells bound to fibronectin-coated surfaces with maximum binding by 1 h at 37 degrees C. There was less attachment to laminin, collagen type I, and collagen type IV. There was no adherence to uncoated surfaces or in the absence of Ca2+. Binding to fibronectin was blocked by a synthetic peptide containing the sequence Arg-Gly-Asp. Therefore, the binding of RBL-2H3 cells to fibronectin may be mediated by surface molecules that belong to the integrin family. Adherence to fibronectin-coated surfaces resulted in cell spreading, a reorganization of the cytoskeletal elements, and a redistribution of the secretory granules. Attachment to fibronectin also dramatically enhanced high affinity IgE receptor-mediated histamine release. This enhancement was maximum by 1 h of adherence and lasted for at least 6 h. There was also enhanced secretion by the Ca2+ ionophore A23187. Thus, adherence to fibronectin can enhance both receptor and non-receptor-mediated release. Addition of soluble fibronectin to RBL-2H3 cells in suspension had no effect on secretion. Therefore, enhanced histamine release required cell attachment to immobilized fibronectin. These results suggest that secretion from mast cells/basophils may be modulated by their interaction with the extracellular matrix.
Cocaine amplifies HIV-1 replication in cytomegalovirus-stimulated peripheral blood mononuclear cell cocultures.
Authors: Peterson P K , Gekker G , Chao C C , Schut R , Verhoef J , Edelman C K , Erice A , Balfour H H 
Published: January 2023

Abstract
Cocaine and CMV each have been suggested to promote the progression of HIV-1 infection. In the present study, the interaction of cocaine and CMV was investigated in a PBMC coculture assay in which release of HIV-1 p24 Ag into coculture supernatants was used as an index of HIV-1 replication. CMV was an effective activation signal for HIV-1 replication when PBMC from CMV-seropositive donors were used in the coculture assay, and cocaine markedly increased replication of HIV-1 in these cocultures. The synergistic activity of cocaine was reduced by neutralizing antibodies to TNF-alpha and by pentoxifylline, an inhibitor of TNF-alpha mRNA production. Also, antibodies to transforming growth factor-beta (TGF-beta) eliminated the amplifying effect of cocaine on HIV-1 replication, whereas antibodies to IL-6 were inactive. The potentiating effect of cocaine could be reproduced by addition of rTNF-alpha or rTGF-beta to the cocultures of CMV-activated PBMC, although TGF-beta was substantially more potent than TNF-alpha. The possibility that TNF-alpha may act indirectly through stimulation of TGF-beta was suggested by the finding of reduced TGF-beta levels in culture supernatants of PBMC that were treated with CMV and cocaine in the presence of antibodies to TNF-alpha. Thus, cocaine amplifies HIV-1 replication in cocultures containing CMV-activated PBMC via a mechanism that appears to involve both TNF-alpha and TGF-beta. The results of this study support the possibility that cocaine and CMV could enhance HIV-1 replication and, thus, aggravate HIV-1-related disease.
Identification of ezrin as an 81-kDa tyrosine-phosphorylated protein in T cells.
Authors: Egerton M , Burgess W H , Chen D , Druker B J , Bretscher A , Samelson L E 
Published: January 2023

Abstract
We have used APT affinity purification to isolate tyrosine-phosphorylated proteins from MRL lpr/lpr (lpr) mouse T cells. One such protein is pp81 ezrin, previously identified as a tyrosine-phosphorylated protein in epidermal growth factor-stimulated A431 carcinoma cells. Biochemical analyses in A431 and gastric parietal cells have revealed ezrin to be a cytoskeleton-associated cytosolic protein. In Jurkat T cells, however, using similar methods we have shown ezrin to be a cytosolic protein with no measurable cytoskeletal association. We also observed no increases in ezrin tyrosine phosphorylation in TCR-stimulated Jurkat T cells, unless the cells were pretreated with protein tyrosine phosphatase inhibitors, suggesting that T cell ezrin tyrosine phosphorylation is tightly controlled by protein tyrosine phosphatases. The fraction of tyrosine phosphorylated ezrin in lpr T cells was 5 to 10 times that observed in Jurkat T cells, which along with constitutive TCR-zeta phosphorylation and pp60fyn overexpression, is a feature of the lpr defect.
Antigen receptor-mediated anergy in resting T lymphocytes and T cell clones. Correlation with lymphokine secretion patterns.
Authors: Williams M E , Shea C M , Lichtman A H , Abbas A K 
Published: January 2023

Abstract
The goal of these studies was to define the stimuli and factors that control the induction of anergy in unimmunized resting T lymphocytes. Initial experiments, aimed at establishing the system, showed that exposure of Th1 but not Th2 clones to immobilized anti-CD3 leads to a block in autocrine growth factor production and proliferation upon subsequent restimulation with Ag+APC. Anergy is not prevented by accessory cells, suggesting that this model of T cell tolerance may be due to receptor-mediated inhibitory signals, independent of costimulatory molecules. Culture of small (resting) unimmunized T lymphocytes with anti-CD3 +/- IL-2 induces unresponsiveness to restimulation with anti-CD3, but culture with anti-CD3+IL-4, which stimulates the differentiation of resting cells into IL-4 producers, does not induce anergy. Thus, IL-4-producing clones and bulk populations of IL-4-producing T cells are resistant to Ag receptor-mediated inhibitory stimuli. These results provide experimental models for studying the mechanisms of anergy in normal, unselected, mature T cells, and demonstrate fundamental similarities between cloned cell lines and unimmunized T lymphocytes in the induction of anergy.
Genomic structure and strain-specific expression of the natural killer cell receptor NKR-P1.
Authors: Giorda R , Weisberg E P , Ip T K , Trucco M 
Published: January 2023

Abstract
NK cells are able to lyse a variety of virally infected and neoplastic cells in an MHC-unrestricted manner. The cell-surface protein NKR-P1 is thought to play a key role in this process. NKR-P1, initially identified in rat IL-2 activated NK cells, is encoded in the mouse by at least three similar, but not identical, genes. We previously reported the isolation and characterization of three different NKR-P1 cDNA, termed cDNA 2, 34, and 40, from IL-2 activated mouse NK cells. This report describes the structure of the gene encoding NKR-P1 cDNA 2, the smallest of these three cDNA. Gene 2 is composed of six exons spanning approximately 14 kb of genomic DNA. The first exon encodes the N-terminal intracellular domain, and exons 4, 5, and 6 contain the sequences coding for the CRD. This organization is similar to that of other genes that encode C-type animal lectins. The expression of the NKR-P1 genes in A-LAK cells from 13 mouse strains was examined by Northern blot analysis. NKR-P1 expression appears to coincide with that of the NK1.1 Ag. This observation further supports the hypothesis that the NK1.1 Ag is encoded by one of the NKR-P1 genes. Nucleotide sequence analysis of the promoter region of the three NKR-P1 genes in BALB/c and C57BL/6 mice suggests that differences in the level of expression probably do not result from alterations in the upstream regions of these genes, but may be caused by the expression of strain-specific transacting factors.
IL-10 induces transcription of the gene for mouse mast cell protease-1, a serine protease preferentially expressed in mucosal mast cells of Trichinella spiralis-infected mice.
Authors: Ghildyal N , McNeil H P , Stechschulte S , Austen K F , Silberstein D , Gurish M F , Somerville L L , Stevens R L 
Published: January 2023

Abstract
Mouse bone marrow-derived mast cells (BMMC) obtained by culturing progenitor cells with rIL-3 express mouse mast cell protease (MMCP)-5 mRNA but not MMCP-1 mRNA or MMCP-4 mRNA. In terms of mast cell differentiation, these transcripts encode one early-expressed and two late-expressed chymases, respectively. cDNA and cRNA probes were used in RNase protection assays and RNA blot analyses to study the expression of these three homologous protease genes in cultured mast cells and in helminth-infected mice. Intestinal tissue from Trichinella spiralis-infected mice, containing high numbers of mucosal mast cells, had abundant amounts of MMCP-1 mRNA but only minimal amounts of the serosal mast cell transcript that encodes MMCP-4. Exposure of mouse BMMC to rIL-10-induced transcription of the MMCP-1 gene but not the MMCP-4 gene, and a cDNA encoding MMCP-1 was obtained from these rIL-10-treated cells. The expression of MMCP-1 mRNA in BMMC depended on the continuous exposure of these cells to rIL-10, and the level of MMCP-1 mRNA (but not MMCP-5 mRNA) was substantially higher in BMMC maintained in rIL-4 and rIL-10 than in rIL-3 and rIL-10 or in rIL-3, rIL-4, and rIL-10. Thus, whereas rIL-3 elicits transcription of early expressed genes in cultured mast cells, it suppresses the transcription of late-expressed genes. These in vitro and in vivo transcription studies also indicate that rIL-10 preferentially induces differentiation of mouse progenitor cells in a mucosal mast cell-specific lineage, and that expression of granule serine protease genes is regulated in a subclass-specific manner in mouse mucosal mast cells and serosal mast cells.
Induction and function of eosinophil intercellular adhesion molecule-1 and HLA-DR.
Authors: Hansel T T , De Vries I J , Carballido J M , Braun R K , Carballido-Perrig N , Rihs S , Blaser K , Walker C 
Published: January 2023

Abstract
We have previously established that eosinophils studied ex vivo from the sputum of asthmatics express intercellular adhesion molecule-1 (ICAM-1) and HLA-DR, whereas peripheral blood eosinophils do not express these surface proteins. On incubation of highly purified (greater than 99.5% pure) blood eosinophils from normal subjects with T cell supernatants, eosinophil ICAM-1 was induced in 24 h, whereas HLA-DR was maximally induced within 48 h. Recombinant cytokines that enable eosinophil survival (IL-5, IL-3, and granulocyte macrophage-CSF) were found to be unable to induce ICAM-1 or HLA-DR, even when pooled at concentrations individually required for eosinophil survival. However, synergy between these eosinophil survival factors and TNF (-alpha and -beta) was found mainly responsible for ICAM-1 induction, whereas synergy between IL-3 and IFN-gamma occurred for HLA-DR induction. Culture of eosinophils in the presence of cytokines and cycloheximide prevented expression of ICAM-1 and HLA-DR, showing that de novo eosinophil protein synthesis is occurring. At a functional level we demonstrate that ICAM-1-bearing eosinophils have increased adhesion capacity for autologous T cells. In contrast, HLA-DR-expressing eosinophils mediated Ag-specific proliferation of an autologous HLA-DR-restricted T cell clone that was inhibitable by anti-HLA-DR and anti-ICAM-1 mAb. Since eosinophil-mediated Ag presentation was inhibitable by treatment of eosinophils with glutaraldehyde or chloroquine, this suggests that eosinophils participate in Ag uptake, processing, and presentation and have accessory functions. Thus, through the induction of ICAM-1 and HLA-DR on tissue eosinophils, eosinophils have the capacity to interact with leukocytes and present Ag to T cells.
Tolerance mechanism in experimental ovarian and gastric autoimmune diseases.
Authors: Smith H , Lou Y H , Lacy P , Tung K S 
Published: January 2023

Abstract
Neonatal splenocytes, neonatal thymocytes, or phenotypically mature adult thymocytes, transferred from normal BALB/c mice to syngeneic athymic nu/nu (or SCID) mice, led to autoimmune oophoritis and autoimmune gastritis, with corresponding serum autoantibodies, in the recipients. The overall disease incidence was 73%; the pathology ranged from mild to severe, with complete loss of ovarian follicles and gastric parietal cells. CD4+ neonatal spleen cells and CD4+ CD8- adult thymocytes were required for autoimmune disease induction. Adult spleen cells did not elicit disease, but they prevented disease when co-transferred with neonatal spleen cells. However, in confirmation of an earlier report by Sakaguchi et al., (J. Exp. Med. 161:72, 1985), a subset of adult splenic T cells expressing a low level of CD5 molecules elicited similar autoimmune diseases. Thus, self-reactive T cells responsible for autoimmune disease of the stomach and ovary are not effectively deleted in the thymus, and they exist in the peripheral lymphoid organs of normal mice. We conclude that the functional expression of the self-reactive T cells is ontogenetically regulated; whereas T cells in the neonatal mice readily elicited autoimmune diseases in nu/nu recipients, regulatory cells may render self-reactive T cells in the normal adults unresponsive.
Administration of anti-CD45 mAb specific for a B cell-restricted epitope abrogates the B cell response to a T-dependent antigen in vivo.
Authors: Domiati-Saad R , Ogle E W , Justement L B 
Published: January 2023

Abstract
CD45 is a receptor-like protein tyrosine phosphatase expressed exclusively by cells of the hemopoietic lineage. Studies in vitro involving treatment of B cells with anti-CD45 mAb have demonstrated that ligand binding to CD45 alters the cell's response to various activation/differentiation stimuli. In general anti-CD45 treatment has been shown to exert an inhibitory effect on early activation events resulting in the failure of quiescent B cells to enter the cell cycle. These studies suggest that CD45 acts as an important regulatory molecule in vitro, that controls B cell function. In contrast, little is known concerning the role that CD45 plays in vivo regarding regulation of B cell activation and differentiation in response to T-dependent Ag. In our study the anti-CD45 mAb RA3.6B2, which recognizes a B cell-restricted epitope, was used to examine this question. Administration of anti-CD45 mAb in vivo was found to inhibit the proliferative response of splenocytes when stimulated with B cell-, but not T cell-specific mitogens. Immunization with the T-dependent Ag FITC-KLH in the presence of increasing amounts of anti-CD45 mAb resulted in a significant, dose-dependent inhibition of the plaque-forming cell response. Additionally, anti-CD45 mAb inhibited the production of FITC-specific serum antibodies indicating that the effect was systemic. Finally, anti-CD45 mAb appeared to exert a maximal effect at earlier time points, within 48 h of Ag administration, suggesting that B cell activation was primarily affected. These results provide evidence to support the conclusion that CD45 is an important regulatory molecule that is involved in the control of B cell activation in vivo.
Naturally processed HLA class I bound peptides from c-myc-transfected cells reveal allele-specific motifs.
Authors: Harris P E , Colovai A , Liu Z , Dalla Favera R , Suciu-Foca N 
Published: January 2023

Abstract
Naturally processed peptides, bound to HLA-A2, A68, B40 molecules, were isolated from a c-myc transfected lymphoblastoid B cell lines for sequence analysis. Forty-three sequences of bound peptides could be grouped into three structural motifs. One of the peptide sequences obtained, SLLPAIVEL, was identical to a previously reported peptide bound to HLA-A2.1 and was used for grouping HLA-A2-bound peptides. A second motif, identical to that previously reported for HLA-A68-bound peptides, was also observed. A distinct third motif, consistent with the structure of the HLA-B40 "45 pocket," was observed. The peptides within this group contained glutamate in position 2, usually followed by a hydrophobic residue in positions 3 and 9. Within this motif group of peptides bound to MHC class I molecules, one peptide, HEETPPTTS, was 100% homologous to residues 243-251 of the c-myc protein.
CD28-mediated costimulation is necessary for the activation of T cell receptor-gamma delta+ T lymphocytes.
Authors: Sperling A I , Linsley P S , Barrett T A , Bluestone J A 
Published: January 2023

Abstract
The role of costimulation in the activation of TCR-gamma delta cells in normal mice and mice transgenic (tg) for a TCR-gamma delta receptor was investigated. Activation of TCR-gamma delta cells required two signals. One signal was mediated by TCR occupancy, whereas a second signal was provided by accessory cells. The importance of the CD28/B7 interaction in the delivery of the second signal was demonstrated in multiple ways. First, addition of a soluble fusion protein homolog of CD28, CTLA4Ig, significantly inhibited the activation of G8 tg splenic TCR-gamma delta lymphocytes and intestinal epithelial TCR-gamma delta lymphocytes by Ag-bearing lymphocytes during primary stimulation. Similarly, both proliferation and IFN-gamma production were inhibited by addition of CTLA4Ig to secondary antigenic stimulation of G8 tg TCR-gamma delta cells. Second, an Ag-bearing thymoma, EL-4, was only able to stimulate expanded G8 tg TCR-gamma delta cells when the thymoma expressed B7. This stimulation was blocked by both CTLA4Ig and anti-B7 antibody. Third, antibodies to CD28 were able to mimic the costimulatory affect of APC. TCR-gamma delta cells cultured with either Ag-bearing fixed stimulator cells or submitogenic concentrations of immobilized anti-pan TCR-gamma delta mAb proliferated only in the presence of anti-CD28 mAb. Finally, G8 tg cells produced IL-2 only in the presence of APC costimulation or anti-CD28 antibodies, and the addition of exogenous rIL-2 overcame the need for costimulation. Thus, autocrine IL-2 production is one of the major consequences of TCR-gamma delta cell costimulation. Together these data demonstrate that costimulation is necessary for the activation of TCR-gamma delta cells and can occur through CD28 interaction.