bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble Fcγ receptors II (FcγRII) are generated by cleavage of membrane FcγRII
Authors: Sautès Catherine , Varin Nadine , Teillaud Christophe , Daëron Marc , Even Jos , Hogarth P. Mark , Fridman Wolf H. 
Published: March 2007

AbstractThis study describes the production of soluble FcγRII by a cell line, D1B1, obtained by transfection of mouse L cells with a murine β1 FcγRII cDNA. Upon incubation at 37 °C, radioiodinated D1B1 cells release a 39‐kDa soluble FcγRII, reacting with the rat anti‐mouse FcγRII monoclonal antibody 2.4G2, and binding to mouse IgG2a, IgG2b and IgG1 but not IgG3. In contrast to the transmembrane 50‐ to 70‐kDa receptor, this soluble FcγRII does not react with antibodies directed against a peptide corresponding to the 15 carboxy‐terminal intracytoplasmic amino acids of β FcγRII. N‐Glycosidase F treatment generates a 18‐kDa polypeptide. A 32‐ to 40‐kDa soluble FcγRII, which resolves into 18.5‐ and 20‐kDa polypeptides after deglycosylation, was also isolated from the culture medium of unlabeled D1B1 cells. Therefore, this study indicates that soluble FcγRII corresponding to the two extracellular domains of FcγRII are generated by cleavage of membrane FcγRII. Proteolysis occurs most probably at the vicinity of the transmembrane region of the receptor, around amino acids 165 to 180.
T cell receptor δ diversity of freshly isolated T lymphocytes in rheumatoid synovitis
Authors: Sioud Mouldy , Førre Øystein , Natvig Jacob B. 
Published: March 2007

AbstractIn some patients with rheumatoid synovitis the distribution of Vδ gene families used by freshly isolated T lymphocytes from the synovial fluid and peripheral blood is different: peripheral blood T lymphocytes preferentially use the Vδ2 gene segment, whereas the majority of synovial fluid T lymphocytes use the Vδ1. The antigenic diversity of T cell receptor γ/δ is mainly dependent upon base sequences in the V‐J junction. In the present study we investigated whether the synovial fluid T lymphocytes expressing the Vδ1 gene segment were derived from a polyclonal or monoclonal expansion. The sequences encoding the V‐J junctions of 11 cDNA clones derived from the synovium of two patients with chronic arthritis were determined. Our data demonstrate that the Vδ1 cDNA clones have different V‐J junction sequences. This indicates that the Vδ1‐expressing T cells found in the synovial compartment are polyclonally expanded.
Influence of I‐E expression on induction of neonatal transplantation tolerance
Authors: Streilein J. Wayne , Socarras Sandra , Powell Thomas J. 
Published: March 2007

AbstractNeonatal transplantation tolerance was one of the first experimental systems to reveal that tolerance could be achieved to non‐self antigens in living animals. Functional and direct evidence (obtained by the use of monoclonal antibodies directed at T cell receptors specifically reactive with I‐E molecules) confirm that tolerance is achieved, at least in part, via clonal elimination of developing thymocytes. In this report, we show that induction of tolerance of class I alloantigens in neonatal mice is governed by expression of I‐E molecules. Neonatal I‐E non‐expressor mice proved to be highly resistant to the acquisition of class I tolerance if the donor inoculum expressed disparate class I antigens as well as I‐E molecules. The spleens of the few class I‐tolerant, I‐E non‐expressor mice that were generated were found to be depleted of I‐E‐reactive (RR315+) T cells, whereas no such depletion was observed in their neonatally injected, but non‐tolerant littermates. By contrast we found no resistance to tolerance of I‐A alloantigens when neonatal I‐E non‐expressor mice received injections of I‐A‐disparate, I‐E‐bearing donor cells. In these tolerant mice, splenic I‐E‐reactive T cells were readily detected in apparently normal amounts. These results indicate that lack of I‐E expression in newborn mice confers resistance to tolerance induction to class I alloantigens, especially when the latter are expressed on donor cells that also display I‐E molecules. The possible mechanisms operating to produce resistance to tolerance induction in neonatal mice are discussed, including the possibilities that (a) I‐E may act as a restricting element during tolerance induction (an ontogenic process), and (b) the expression of I‐E on H‐2‐disparate, I‐E‐expressing test skin allografts may provide a source of “help” for CD8+ cytotoxic T cell precursors, leading to graft rejection.
Analysis of a positive feedback mechanism in the anti‐Sm autoantibody response of MRL/MPJ‐lpr/lpr mice
Authors: Stocks Martin Robert , Williams David Gareth , Maini Ravinder Nath 
Published: March 2007

AbstractThe mechanism of induction of anti‐Sm antibodies by passive transfer of anti‐Sm mAb in MRL/lpr mice was investigated. No idiotypic relationship was detected between the inducing monoclonal antibody KSm2 and either the induced circulating anti‐Sm antibodies or the products of anti‐Sm‐producing hybridomas derived from spleen cell fusion of treated mice. Treatment of mice with ribonucleoprotein Sm antigen, alone or as an immune complex, induced anti‐Sm and anti‐ribonucleoprotein antibodies similarly to treatment with KSm2. This suggests that autoantigen contributes to the development of the anti‐Sm response in MRL mice.
Age‐related changes in lymphokine production related to a decreased number of CD45RBhi CD4+ T cells
Authors: Nagelkerken Lex , Hertogh‐Huijbregts Anita , Dobber Ruud , Dräger Angelika 
Published: March 2007

AbstractThe ability of CD4+ T cells from CBA/Rij mice to produce interleukin (IL) 2 after stimulation with anti‐CD3, concanavalin A, or the combination of phorbol 12‐myristate 13‐acetate and ionomycin declines during aging. This phenomenon was accompanied by an increased production of IL 4 and interferon‐γ. These age‐related changes in lymphokine production correlated with the decrease in the percentage of CD45RBhi CD4+ T cells from about 80% in 2‐month‐old to about 40% in 27‐month‐old mice. This phenotypic shift was responsible for the decline in IL 2 production, because in young and in old mice CD45RBhi CD4+ T cells were more potent IL 2 producers than CD45RBlo cells. Moreover, old CD45RBhi CD4+ T cells produced less IL 2 than their young counterparts. Proliferative responses by T cells from old mice were lower than those of young mice, regardless whether the cultures were supplemented with IL 2, IL 4 or both lymphokines. As far as CD4+ T cells were concerned, this hyporesponsiveness was found in the CD45RBlo as well as in the CD45RBhi CD4+ T cell population.
Elevated levels of intracellular cAMP sensitize resting B lymphocytes to immune complex‐induced unresponsiveness
Authors: Stein Sidney H. , Phipps Richard P. 
Published: March 2007

AbstractThe ability of immune complexes (IC) to regulate B lymphocyte differentiation was investigated. Using an in vitro model, we previously demonstrated that macrophages (MΦ) or lymphoid dendritic cells pulsed with IC differentially regulated B cell function, inducing unresponsiveness or stimulation, respectively. The capacity of MΦ to induce unresponsiveness was dependent upon two signals, an antigen‐specific one supplied by the IC and MΦ‐secreted prostaglandin (PG)E2. Total inhibition of antibody production was never achieved as a small percentage of B lymphocytes were resistant to IC‐induced unresponsiveness. In this study, utilizing an accessory cell‐free system, we demonstrate that splenic B cell fractions separated on Percoll density gradients are heterogeneous in their sensitivity to IC‐mediated unresponsiveness. Small resting B lymphocytes are exquisitely sensitive to IC‐mediated negative signaling and exhibit virtual total ablation of antibody responses. Conversely, large activated B cells are more refractory to this inhibitory pathway. PGE2 and other agents which elevate cAMP potentiate IC‐induced unresponsiveness in resting, but not activated B lymphocytes. In addition treatment of resting B cells with PGF2α, which did not elevate cAMP, failed to sensitize these cells to IC‐mediated negative signaling. Unresponsiveness induced by IC is selective for specific aspects of B lymphocyte activation, since B cell differentiation but not proliferation is affected. Furthermore, pre‐treatment of resting B lymphocytes with interleukin 4 prevents the IC‐induced ablation of IgM antibody responses. Overall, our results indicate that the binding of IC by resting B lymphocytes provides a potent mechanism for inhibiting differentiation without affecting proliferation. These observations suggest that in vivo, IC play an important role in regulating the memory B lymphocyte pathway.
Formation of covalently linked C3‐C3 dimers on IgG immune aggregates
Authors: Barrio Elena , Antón Luis C. , Marqués Guillermo , Sánchez Angel , Vivanco Fernando 
Published: March 2007

AbstractUpon activation of the complement system by IgG immune aggregates several components become tightly bound to the aggregates. The covalent interaction of C3 with immune complexes is essential for the solubilization and inhibition of immune precipitation of the complexes. It has recently been reported that on erythrocytes that have a fixed complement, activated C3 can become involved in the formation of C3b‐C3b covalent dimers, which act as high‐affinity binding sites for C5 (Kinoshita, T., Takata, Y, Kozono, H., Takeda, J., Hong, K. and Inoue, K., J. Immunol. 1988. 141: 3895). To characterize the molecular composition of immune aggregates that have fixed complement by the alternative pathway, we have investigated whether such C3b‐C3b dimers are formed in IgG immune complexes. For this purpose immune aggregates bearing covalently bound C3 were analyzed by two‐dimensional gel electrophoresis and the resolved bands transferred to polyvinylidene difluoride membranes and sequenced. When immune aggregates were incubated with serum for 15 min at 37 °C, the major high‐molecular mass bands detected by gel electrophoresis corresponded to heavy chain‐C3α65 and C3α65‐C3α43 (derived from iC3b‐iC3b‐IgG) covalent complexes. If K76COONa, an inhibitor of factor I, was added to the serum, before incubation with the immune complexes, then the major C3α fragment detected on the complexes corresponded to the C3α′ chain (105 kDa) and not C3α65. Hence C3b‐C3b covalent dimers are readily formed on the immune aggregates incubated with normal human serum, and are degraded to iC3b‐iC3b by factor I. The second C3b molecule was shown to be bound to the C3α43 region (C‐terminal portion of the C3α′ chain) of the first C3b molecule, which was itself covalently bound to the heavy, chain of IgG. Covalent complexes of heavy chain‐(C3α65)2 molecular composition were also detected, but their precise bonding pattern has not been established.
Anti‐CD3‐induced cell death in T cell hybridomas: mitochondrial failure and DNA fragmentation are distinct events
Authors: Vukmanović Stanislav , Zamoyska Rose 
Published: March 2007

AbstractTriggering of the T cell receptor of T cell hybridomas leads to interleukin (IL) 2 secretion, inhibition of spontaneous growth, degradation of genomic DNA and cell death. We have investigated the relationship between the ability of mitochondria to convert 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), DNA fragmentation and growth arrest in hybridomas stimulated with anti‐CD3/T cell receptor antibodies. We describe a variant T hybridoma whose mitochondrial function remains unaffected upon stimulation with anti‐CD3 antibody, although it does undergo DNA fragmentation. By contrast, treatment of another anti‐CD3‐stimulated T hybridoma with endonuclease inhibitor completely inhibits the DNA fragmentation response but not mitochondrial failure induced by anti‐CD3 antibody. Thus, we have been able to dissociate anti‐CD3‐induced mitochondrial failure and DNA fragmentation, suggesting that they are separate events. Although both undoubtedly contribute to cell death induced by activation the primary cause of death may be mitochondrial failure rather than DNA fragmentation.
Genetic reconstitution of the T cell receptor (TcR) α/β heterodimer restores the association of CD3 ζ2 with the TcR/CD3 complex
Authors: Blumberg Richard S. , Sancho Jaime , Ley Steven C. , McDermott Francis V. , Tan Kut‐Nie , Breitmeyer James , Terhorst Cox 
Published: March 2007

AbstractThe cell surface expression of the T cell receptor (TcR)/CD3 complex and, consequently, the functional competence of the cell is partly dependent on CD3ζ. In its absence, a pentameric complex (TcR α/β/CD3γδϵ) is formed which is inefficiently transported to the cell surface. Reconstitution of CD3ζ by transfection, in turn, restores the cell surface expression and function of the complex. Through the use of transfection experiments, we here provide direct evidence that the association of CD3 ζ2 with the TcR/CD3 complex is dependent on the presence of both the TcR α and β polypeptide chains. Despite wild‐type levels of the CD3ζ protein in a TcR α‐negative mutant human T cell line, a complex was formed intracellularly which lacked CD3 ζ2 and consisted of βγδϵ and β2γδϵ. Upon transfection of the mutant with a TcR α cDNA, a TcR/CD3 complex which contained CD3 ζ2 was observed intracellularly. In contrast to the partial subcomplex on the cell surface of the untransfected cell line, the TcR/CD3 complex on the transfectant was functional as demonstrated by its ability to mobilize intracellular calcium after stimulation with a mitogenic CD3 ζ‐specific monoclonal antibody. Transient transfection studies performed in COS cell fibroblasts indicated that CD3 ζ2 was not interacting with the TcR α protein alone, implying that a conformation provided by either the TcR α/β heterodimer or the TcR α/β/CD3 γδϵ complex was necessary for the association of CD3 ζ2. Transfection studies performed in a TcR α/β‐negative murine T‐T hybridoma confirmed the requirement of both the TcR α and β proteins in CD3 ζ2 binding. We conclude that the TcR α and β chains harbor polypeptide sequences essential for the association of CD3 ζ2 with the TcR/CD3 complex.
Effect of bacterial toxins on human B cell activation. II. Mitogenic activity of the B subunit of cholera toxin
Authors: Dugas Bernard , Paul‐Eugène Nathalie , Génot Elisabeth , Mencia‐Huerta Jean Michel , Braquet Pierre , Kolb Jean Pierre 
Published: March 2007

AbstractThe B subunit of cholera toxin (CT) but not the entire CT was found to induce the proliferation of resting human B lymphocytes. A significant mitogenic effect was observed for B subunit concentrations > 1 μg/ml and reached a maximum of stimulation at 10 μg/ml. As already described for B lymphocytes preactivated with Staphylococcus aureus Cowan Strain I (SAC), B lymphocytes preactivated with the B subunit of CT, but not with the entire CT, were able to proliferate in response to exogenous interleukin 2 (IL 2) and to the low‐molecular weight B cell growth factor (BCGF).To determine the transmembrane signaling system used by the B subunit of CT to mediate its biological effects, we compared the transmembrane signals used by the entire CT, its B subunit and SAC. In comparison to the entire CT, which directly activates adenylate cyclase and increases intracellular cAMP levels, neither the B subunit nor SAC modified the cAMP content. In contrast, although SAC induced inositol phosphate generation neither CT nor the separate subunits were able to induce such a production. Moreover, changes in the fluorescence of indo‐1‐loaded B lymphocytes revealed that mitogenic doses of either the B subunit or SAC induced a rapid and sustained increase in cytoplasmic free Ca2+ concentration ([Ca2+]i). The effect of the B subunit appeared to be largely dependent on the presence of extracellular Ca2+, because in Ca2+‐free medium no [Ca2+]i uptake was observed. In contrast, the SAC‐induced [Ca2+]i uptake is substantially, but not totally, inhibited in Ca2+‐free medium, suggesting that part of the rise in [Ca2+]i was due to the release from internal stores. Moreover, fluorimetric measurements on loaded cells with 2′,7′‐bis(carboxyethyl)‐5(6′)‐carboxyfluorescein revealed that SAC induced a rapid cytoplasmic alkalinization via activation of Na+/H+ exchange, whereas the entire CT and its B subunit had no effect on intracellular pH. Taken together, these data suggest that, in comparison to SAC, the mitogenic effect of the B subunit of CT was mediated through different intracellular biochemical pathways.
Expression of a novel type of immunoglobulin Cλ transcripts in human mature B lymphocytes producing χ light chains
Authors: Guglielmi Paul , Davi Frédéric 
Published: March 2007

AbstractOrdered rearrangement of immunoglobulin genes (heavy chain then χ and eventually λ genes) is observed during B lymphocyte ontogeny. Unexpectedly, we found that human mature B cells producing χ chains and having germ‐line λ genes contain λ mRNA consisting of an invariant 5′ region (herein termed X) and of one of the classical Cλ exons. The X region of these transcripts originates from a unique exon located 5 kb upstream of the J‐Cλ1 gene segment. X‐Cλ mRNA expression occurs without somatic DNA rearrangement. The use of the X DNA fragment as a probe allows definition of a family of human genes that comprises at least four members and includes the first exon of the λ14.1 gene. The latter is selectively transcribed in pre‐B lymphocytes and directs the synthesis of a λ‐like chain. In contrast, the X‐Cλ transcripts do not appear to encode a Cλ‐related polypeptide in mature B cells. Thus, despite a 73% homology extending far beyond the exon sequences, the X and λ14.1 genes are expressed at different stages of B cell development and might serve different functions.
Reticular cells in peripheral lymphoid tissues express the phosphatidylinositol‐linked BP‐3 antigen
Authors: McNagny Kelly M. , Bucy R. Pat , Cooper Max D. 
Published: March 2007

AbstractThe murine BP‐3 antigen was initially described as a variably glycosylated cell surface protein of Mr 38000 to 48000 on lymphoid and myeloid cells. In the present experiments we found that this antigen is released from the surface of pre‐B cells and macrophages by treatment with phosphatidylinositol‐specific phospholipase C (PI‐PLC), suggesting a glycosyl‐phosphatidylinositol (GPI) linkage with the plasma membrane. When the tissue distribution of the BP‐3‐reactive cells was examined by immunohistology, high levels of the antigen were observed on brush borders of the intestinal epithelial cells, within collecting tubules of the kidney and on a subpopulation of reticular cells located in lymph nodes, Peyer's patches and the white pulp areas of the spleen. In contrast, reticular cells located in the thymus, bone marrow and splenic red pulp did not express the BP‐3 antigen. Ontogenic studies revealed that BP‐3 was expressed by the reticular cells in peripheral lymphoid tissues in the neonatal period near the time of lymphocyte immigration into these organs. BP‐3+ reticular cells were observed in the collapsed periarterial lymphatic sheaths of adult mice depleted of T and B cells by cyclophosphamide treatment and in mice with severe combined immunodeficiency (scid), indicating that development of this reticular network is lymphocyte independent. The BP‐3 antigen on the splenic reticular cells was also GPI anchored but its glycosylation pattern differed from that of the BP‐3 molecules on pre‐B cells. A special subpopulation of reticular cells is thus marked by the BP‐3 antigen, and the distribution and biochemical properties of the molecule make it an attractive candidate for a role in lymphocyte‐stromal interactions in the peripheral lymphoid tissues.
CD3+ T cells in severe combined immune deficiency (scid) mice. I. Transferred purified CD4+ T cells, but not CD8+ T cells are engrafted in the spleen of congenic scid mice
Authors: Rudolphi Angelika , Spieß Sibylle , Conradt Peter , Claësson Mogens H. , Reimann Jörg 
Published: March 2007

AbstractYoung (< 3 months of age) and old (> 1 year of age) C.B‐17 scid/scid mice were tested for the presence of immunoglobulin in serum and CD3+ T cells in spleen and peritoneal cavity. In all old severe combined immune deficiency (scid) mice tested we found detectable, but very variable levels of serum immunoglobulin as well as splenic and peritoneal CD3+ T cells comprising 3% to 10% of the nonfractionated cell populations of these organs (n = 10). In contrast, none of the analyzed young scid mice showed any evidence of peripheral lymphocytes. Low numbers (2 × 105 to 5 × 105 cells/mouse) of highly purified CD4+ cells from congenic C.B‐17 or BALB/c donor mice were injected intravenously into young scid recipient mice. A CD4+ T cell population was clearly engrafted when transplanted scid mice were analyzed 8 to 13 weeks after T cell transfer: (a) a CD3+CD4+CD8− T cell population was detectable in the spleens of all recipient scid mice by flow microfluorometry analyses; (b) CD3+CD4+CD8− T cell lines could be grown out of these spleens in vitro; (c) the histological examination revealed evidence of lymphoid cell repopulation in the spleens of all transplanted scid mice and (d) transplanted CD4+ T cell populations could be serially transferred into secondary and tertiary recipient scid mice. These data indicate that scid mice can be constructed in which only the CD4+ T cell compartment is selectively reconstituted. In contrast to the successful engraftment of CD4+ T cell, highly purified congenic CD8+ T cells could not be engrafted into the spleen of scid mice.
Exacerbation of experimental murine cutaneous leishmaniasis with CD4+Leishmania major‐specific T cell lines or clones which secrete interferon‐γ and mediate parasite‐specific delayed‐type hypersensitivity
Authors: Titus Richard G. , Müller Ingrid , Kimsey Paul , Cerny Andreas , Behin Reza , Zinkernagel Rolf M. , Louis Jacques A. 
Published: March 2007

AbstractLeishmania major‐specific T cell lines were derived from mice sensitized to the parasite. The cells were of the CD4+ T cell lineage and, upon adoptive transfer, were found to be capable of inducing parasite‐specific delayed‐type hypersensitivity. Adoptive transfer of these L. major‐specific T cells to syngeneic recipients which were either normal, T cell deficient or B cell and antibody deficient led to exacerbation of infection upon subsequent challenge with L. major. This suggested that host T cells, B cells and antibody were not required for the L. major‐specific T cells to exert their exacerbative effect on the course of cutaneous leishmaniasis. Additional studies revealed that the adoptive transfer of graded doses of these L. major‐specific T cells always resulted in exacerbation of infection. Study of the localization pattern of the cells following transfer showed that they migrate preferentially to the site of the lesions. Furthermore, although the induction phase of this phenomenon was immunologically specific, its effector phase was not.Finally, T cell clones were derived from the L. major‐specific T cell lines. The Tcell clones were phenotypically and functionally identical to the T cell lines from which they were derived. Adoptive transfer of these parasite‐specific Tcell clones to normal syngeneic recipients induced an exacerbated course of infection with L. major. Interestingly, when these cloned T cells were specifically activated in vitro, the cells produced interleukin 2 and interferon‐γ, but no interleukin 4, indicating that they belong to the murine Th1 subset of CD4+ T cells.