bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of somatic mutation in a χ light chain transgene
Authors: Sharpe Melanie J. , Neuberger Michael , Pannell Richard , Azim Surani M. , Milstein César 
Published: March 2007

AbstractAnalysis of mice transgenic for immunoglobulin genes should allow definition of the cis‐acting DNA sequences required to target somatic mutation to antibody V genes. We have looked for mutations in a chimeric χ transgene encoding a V region specific for the hapten 2‐phenyloxazolone (phOx) linked to a rat Cχ gene. Two independent lines of transgenic mice were hyperimmunized with phOx and splenic hybridomas established. In B cells that had been selected by antigen and which used mouse anti‐phOx genes, the endogenous sequences were found to be mutated whereas the transgene remained unchanged. These results suggest either that (a) if the transgene is a “passenger” gene expressed at a low level, transgene mutation is a rare event, or that (b)sequences far from the χ coding region are necessary to direct somatic mutation.
Human T cell proliferative responses to Plasmodium vivax antigens: evidence ofimmunosuppression following prolonged exposure to endemic malaria
Authors: Goonewardene Renu , Carter Richard , Priyntha Gamage C. , del Giudice Giuseppe , David Peter H. , Howie Sarah , Mendis Kamini N. 
Published: March 2007

AbstractHuman T cell proliferative responses, of 33 adult Sri Lankans convalescing from Plasmodium vivax infections, to several P. vivax antigens (i.e. a soluble extract of asexual erythrocytic stage parasites and two cloned antigens that are potential vaccine candidates PV200 and GAM‐1) were assessed. The peripheral blood mononuclear cell proliferative responses to the soluble extract of P. vivax, as assessed by studying both the proportion of responders and the degree of the response, were significantly lower in a group of individuals resident in a malaria endemic area in Sri Lanka than in another group that did not have a life‐long exposure to malaria but had acquired the disease on a visit to an endemic region. Individuals of both groups responded equally well tomitogen. The responses to a non‐malarial antigen such as purified protein derivative of tuberculin were only marginally lower in residents of the malaria‐endemic region. These findings suggest that exposure to endemic P. vivax malaria leads to a specific immuno‐suppression to P. vivax antigens. Immunosuppression of a much lower degree was evident to a non‐malarial antigen.
The cytoplasmic domain of CD4 is required for stable association with the lymphocyte‐specific tyrosine protein kinase p56lck
Authors: Veillette André , Sleckman Barry P. , Ratnofsky Sheldon , Bolen Joseph B. , Burakoff Steven J. 
Published: March 2007

AbstractThe CD4 T cell surface molecule binds MHC class II determinants expressed on antigen‐presenting cells. CD4 is thought to enhance T cell activation by serving as an adhesion molecule as well as possibly by transducing an independent intracellular signal during the process of antigen stimulation. The recent observation that CD4 is physically associated with the Src‐related tyrosine protein kinase p56lck suggests thattyrosine phosphorylation might be involved in these CD4 “signaling” events. The results presented in this report demonstrate that deletion of the cytoplasmic domain of CD4 significantly diminishes its ability to stably associate with p56lck. Thisobservation provides a biochemical basis for the decreased ability of this mutant CD4 molecule to enhance T cell activation during suboptimal antigen stimulation.
Anti‐immunoglobulins induce death by apoptosis in WEHI‐231 B lymphoma cells
Authors: Benhamou Laure E. , Cazenave Pierre‐andré , Sarthou Pierre 
Published: March 2007

AbstractAnti‐membrane immunoglobulin (anti‐mIg) antibodies exert inhibitory effects in immature B lymphocytes such as WEHI‐231 cells. We show here that anti‐mIg treatment causes DNA fragmentation (apoptosis) in these cells. We also report thatco‐treatment with the protein kinase C activator phorbol 12‐myristate 13‐acetate prevents apoptosis induced by anti‐mIg. These results are in agreement with our initial proposal that sensitivity to the toxic effects of anti‐mIg reflects, at least partially, altered signal transduction in immature B lymphocytes. Variations in signal transduction pathways during B lymphocyte ontogeny may, therefore, play a critical role in determining whether B cells should be activated or inhibited via their mIg.
A physical map and analysis of the murine Cχ‐RS region show the presence of a conserved element
Authors: Müller Brigitte , Stappert Heike , Reth Michael 
Published: March 2007

AbstractLambda‐producing B lymphocytes have frequently deleted one or, more often, both Igχ loci. This deletion is mediated by the rearrangement of an element which lies 3′ of Cχ and which is called RS (recombining sequence) in the mouse and Kde (kappa‐deleting element) in the human. The tight correlation between Vλ to Jλ rearrangements and an RS‐mediated deletion may indicate that sequences in the Cχ‐RS region are controlling the activation of the Igλ locus. We have linked the Cχ exon and the RS element byphage cloning and compared the Cχ‐RS region to the previously cloned human Cχ‐Kde region. The distance between Cχ and RS is 25 kb and is thus similar to the distance of 24 kb separating the human Cχ exon and Kde element. Both mouse and man carry a conserved sequence of 470 bp (Rx) which lies 9 kb 3′ of the mouse Cχ and 12 kb 3′ of the human Cχ exon. The conserved mouse Rx sequence contains part of the χ3′ enhancer.
CD43 (leukosialin, sialophorin, large sialoglycoprotein) can be expressed in both normal and Wiskott‐Aldrich fibroblasts via transfection of a leukosialin cDNA
Authors: Pallant Adam , Fukuda Minoru , Frelinger John G. 
Published: March 2007

AbstractHuman leukosialin is among the most abundant sialoglycoproteins found on the surface of cells of the lympho‐hematopoietic system. Leukosialin, also known as sialophorin, is involved in T cell proliferation, and its molecular isoform changes upon cellular activation. We show that human leukosialin is identical to the antigens described by the monoclonal antibodies (mAb) G10‐2, G19‐1 (CD43) and B1B6 (large sialoglycoprotein). This identity was suggested by immunoblot analysis of transformed cell lysates. Further, fibroblasts transfected with the human leukosialin cDNA gain reactivity to these mAb, showing conclusively that molecules recognized by these mAb are determined by the same cDNA. Expression of the leukosialin gene is readily detected on the surface of transfected human and mouse fibroblasts. Immunoblot analysis of the transfectants indicates that processing of the human protein occurs in both species. Alterations of leukosialin expression have been reported in patients with the Wiskott‐Aldrich Syndrome (WAS), an X‐chromosome‐linked immunodeficiency disease. While essentially all of the transfected tumor and primary fibroblasts from normal individuals express the transfected gene on the cell surface, only half of the transfected Wiskott‐Aldrich fibroblasts express CD43. Nonetheless, the antigenic pattern by immunoblot analysis of both normal and WAS‐transfected fibroblasts appears identical. These results indicate that WAS‐derived cells can express leukosialin and that the product of WAS X‐chromosome mutation may not be expressed in fibroblasts.
A malaria heat‐shock‐like determinant expressed on the infected hepatocyte surface is the target of antibody‐dependent cell‐mediated cytotoxic mechanisms by nonparenchymal liver cells
Authors: Rénia Laurent , Mattei Denise , Goma Joseph , Pied Sylviane , Dubois Philippe , Miltgen François , Nüssler Andreas , Matile Hugues , Menégaux Fabrice , Gentilini Marc , Mazier Dominique 
Published: March 2007

AbstractCultured hepatic stages of Plasmodium falciparum and P. yoelii and with a monoclonal antibody recognizing a C‐terminal fragment of the P. falciparum heat‐shock‐like protein (Pfhsp70) revealed that synthesis of this antigen first occurs during intrahepatic development of the parasite, at the two nuclei stage. Using a variety of techniques, including scanning electron microscopy, we observed that this antigenic determinant was expressed on the infected hepatocyte membrane. Its participation in antibody‐dependent cell‐mediated cytotoxicity was investigated. While no effect was obtained with peripheral blood cells, we found that 25% of the schizonts were specifically lysed when using spleen cells at a killer/target ratio of 30/1. More interestingly, with nonparenchymal liver cells, up to 50% of the hepatic parasites disappeared with a killer/target ratio of 10/1.
Modulation of immune responses with monoclonal antibodies. I. Effects on regional lymph node morphology and on anti‐hapten responses to haptenized monoclonal antibodies
Authors: Mjaaland Siri , Fossum Sigbjøm 
Published: March 2007

AbstractRepeated injections of monoclonal antibody (mAb) culture supernatants into rat footpads increased the weights of the draining lymph nodes. Immunostained freeze sections showed that injection of MRC OX2, a mAb reacting with rat follicular dendritic cells and MRC OX7 (anti‐Thy‐1.1), led to gross hypertrophy primarily of the follicular areas, whereas MRC OX6 (anti‐rat major histocompatibility complex class II molecules) resulted in selective stimulation of the paracortex. These findings indicate that mAb, when conjugated to certain antigens, would modulate the immune response to these antigens. Consequencly, the mAb were conjugated with fluorescein isothiocyanate (FITC) and the humoral response against the hapten measured. The primary anti‐FITC antibody response was tenfold stronger than after stimulation with FITC conjugated to a conventional carrier such as ovalbumin, and had some characteristics of a secondary response: a fast increase of IgG level to very high titers and a long duration without further amplification at later antigen challenges.
Clonal anergy in self‐reactive α/β T cells is abrogated by heat‐shock protein‐reactive γ/δ T cells in aged athymic nude mice
Authors: Yuuki Hiroyuki , Yoshikai Yasunobu , Kishihara Kenji , Iwasaki Akinori , Matsuzaki Goto , Takimoto Hiroaki , Nomoto Kikuo 
Published: March 2007

AbstractAlthough T cells proliferate and differentiate primarily in the thymus, athymic nude mice contain an appreciable level of T cell receptor α/β and γ/δ T cells, suggesting the existence of the extrathymic pathway in the development of both T cells. Recent studies with nude mice indicate that clonal deletion of self‐reactive T cells does not occur extrathymically. In the present study, we have investigated the responsiveness of self‐reactive T cells differentiating along an extrathymic pathway in aged BALB/c (H‐2d, Mls‐1b2a, I‐E+, 7–8 month old) nude mice. Consistent with recent reports, T cells bearing Vβ3 or Vβ11, which are important for recognizing proteins encoded by the Mls‐2a or the I‐E allele, respectively, are readily detected in age nude mice. The Vβ3‐ or Vβ11‐bearing T cells, however, do not proliferate in response to staphylococcal enterotoxin A which specifically stimulates Vβ3‐ or Vβ11‐bearing T cells. When exogenous recombinant interleukin 2 was added to the culture, the Vβ3‐bearing T cells in aged nude mice significantly proliferated in response to staphylococcal enterotoxin A. Aged nude mice also contained a substantial level of γ/δ T cells which account for 15.6% of all Thy‐1.2+ cells. The γ/δ T cells proliferated and produced a significant level of interleukin 2 in response to the 65‐kDa mycobacterial heat‐shock protein, which is highly homologous to its eukaryotic counterpart. These results suggest that unresponsiveness of self‐reactive T cells may be reversed by T cells responding to stress proteins expressed by the invading microbes and/or the stressed autologous cells.
Thy‐1‐specific helper T cells can provide intramolecular help, but can provide intermolecular help only if the phosphatidylinositol anchor of Thy‐1 is replaced by a membrane insert
Authors: Stauss Hans , Mitchison N. Avrion , Yao Michelle 
Published: March 2007

AbstractWe have investigated the ability of Thy‐1 to serve as a helper antigen in delivering intermolecular help. The parental Thy‐1 molecule, which is attached to the cell surface via a phosphatidylinositol anchor, failed to deliver intermolecular help for an antibody response to H‐2 alloantigens. This failure appears to be due to the phosphatidylinositol anchor since a Thy‐1 hybrid construct, which is expressed as a transmembrane cell surface molecule, can serve as helper antigen and deliver intermolecular help.
The rat B cell system: The anatomical localization of flow cytometry‐defined B cell subpopulations
Authors: Kroese Frans G. M. , Butcher Eugene C. , Lalor Paul A. , Stall Alan M. , Herzenberg Leonore A. 
Published: March 2007

AbstractTwo‐color flow cytometrical (FCM) analysis of rat peripheral lymphoid organs shows two distinct IgM/IgD‐defined B cell subpopulations, similar to those of the mouse: a major population of cells expressing little IgM and high levels of IgD (population I) and a minor population of cells expressing high levels of IgM but little IgD (population III). In peripheral lymphoid organs population III cells are mainly found in spleen where they represent about 25% of the B cells; population III cells are almost absent from lymph nodes and Peyer's patches. In adult bone marrow and in neonatal spleen the majority of IgM/IgD‐defined B cells (> 70%) are population III cells, similar to what is observed in the mouse. In contrast with mice, only a low proportion of the cells (1%) recovered from the peritoneal cavity are B cells, and most of them belong to population I.Previously defined monoclonal antibodies (HIS22 and HIS24) to B cell forms of the leukocyte common antigen (CD45R) in combination with staining for surface IgM and surface IgD demonstrates a further heterogeneity of rat B cells by three‐color FCM analyses. HIS22 labels most population I cells; population III cells and a small subset (about one third) of population I express only very low levels of the HIS22 determinant. HIS24 reacts with population I cells and subdivides population III into two subsets: about one third of splenic population III cells are brightly stained with this antibody whereas fluorescence of the remaining two‐thirds is lower. The HIS24bright population III cells likely are newly formed B cells since cells with this phenotype are the predominant surface Ig population found in adult bone marrow and neonatal spleen.In tissue sections of lymphoid organs, HIS22‐ and HIS24‐positive cells are mainly found in lymphoid follicles; splenic marginal zones are almost unstained. Combining immunohistological analysis with the FCM data, we therefore conclude that the small follicular B cells are in population I and marginal zone B cells are found in the HIS24dull population III. The in situ localization of HIS24bright population III cells and the HIS22dull population I cells is not clear.Based upon the relative expression of surface markers on B cells we propose a model of B cell differentiation in the rat in which a common precursor cell (the HIS24bright population III cell), produced in the bone marrow, enters the spleen and leads to two distinct B cell differentiation pathways: one leading to marginal zone B cells and the other giving rise (through an intermediate cell type) to the majority of B cells, the small resting follicular B cells.
Cytotoxic α/β+ and γ/δ+ T cells in murine intestinal epithelium
Authors: Viney Joanne L. , Kilshaw Peter J. , MacDonald Thomas T. 
Published: March 2007

AbstractMurine intraepithelial lymphocytes (IEL) consist of two main populations. Approximately half are Thy‐1+, most of which are CD3+, T cell receptor (TcR) α/β+, and the remainder are Thy‐1−, most of which are CD3+, TcR α/β (presumably TcR γ/δ+). In redirected cytotoxicity assays, TcR α/β+ IEL are potent cytotoxic effectors. Thy‐1−, CD3+, TcR α/β− IEL isolated from athymic mice are also cytotoxic. Thus, regardless of TcR usage or Thy‐1 expression, IEL are cytotoxic effectors.
Monoclonal antibody against α(1 → 3) dextran transfers suppression of the immune response to the acetylcholine receptor
Authors: Tong Zhou , Dwyer Donard S. 
Published: March 2007

AbstractPrevious studies have demonstrated that immunization of BALB/c mice with α(1 → 3) dextran (Dex) is accompanied by a reduction in the subsequent immune response to the acetylcholine receptor (AChR), depending on the timing of the Dex administration relative to AChR challenge. Here, we report that suppression of the anti‐AChR response can be transferred by a monoclonal antibody, known as DX2, which is specific for Dex. Serum transfer experiments have also supported the notion that antibody is important for this effect. In addition, two new idiotypic markers have been defined that are expressed mainly by antibodies against Dex, including DX2. The anti‐idiotypic reagents (Sh135 and EB5) are derived from the immune response to the AChR. A human monoclonal antibody which binds to Dex (SR 11) resembles the BALB/c antibodies that are involved in the suppression of the anti‐AChR response. These findings emphasize the functional relevance of the AChR‐Dex network not only for the BALB/c immune response to the AChR, but also for humans with the autoimmune disease, myasthenia gravis.
Persistence of anti‐donor allohelper T cells after neonatal induction of allotolerance in mice
Authors: Abramowicz Daniel , Vandervorst Philippe , Bruyns Catherine , Doutrelepont Jean‐Marc , Vandenabeele Peter , Goldman Michel 
Published: March 2007

AbstractBALB/c mice rendered tolerant to A/J alloantigens by neonatal injection of 108 (A/J × BALB/c)F1 spleen cells develop an autoimmune disease associated with a polyclonal activation of donor B cells. To study the mechanisms leading to donor B cell activation in tolerant mice, we prepared mixed lymphocyte cultures (MLC) between splenic T cells from neonatally injected mice and donor‐type (A/J × BALB/c)F1 or third‐party (C57BL/6 × BALB/c)F1 B cells. T cells from tolerized mice were unable to generate cytotoxic T lymphocytes, to proliferate or to secrete interleukin (IL)2 after stimulation with donor alloantigens in MLC. These T cell responses were present after MLC with third‐party antigens, but were of lower intensity than those generated by control BALB/c T cells. In contrast. T cells from tolerized mice stimulated immunoglobulin production by donor‐type (A/J × BALB/c)F1 B cells much more powerfully than T cells from control BALB/c mice. The stimulation of donor‐type (A/J × BALB/c)F1 B cells was polyclonal, as attested by the levels of anti‐hapten and anti‐DNA antibodies in the MLC supernatants. IgM was the dominant isotype secreted in vitro, but IgG1 and IgG3 were also produced in significant amounts. Lysis experiments indicated that the T cells responsible for F1 B cell stimulation in MLC were CD4+ host T cells. These T helper cells were alloreactive since they did not stimulate syngeneic BALB/c B cells, and their effect on donor B cells was specifically blocked by anti‐donor Ia monoclonal antibodies. Addition of anti‐IL 4 monoclonal antibody to MLC between T cells from tolerant mice and (A/J × BALB/c)F1 B cells almost completely abolished the production of IgG1, but not that of IgM or IgG3. Taken together, these findings indicate that neonatal injection of alloantigens in BALB/c mice induces a state of dissociated tolerance, with unresponsiveness of anti‐donor T cells secreting IL 2 on the one hand, and persistence of T cells responsible for B cell help and IL 4 secretion on the other hand.
Cytokine‐induced generation of multinucleated giant cells in vitro requires interferon‐γ and expression of LFA‐1
Authors: Möst Johannes , Neumayer Heinz P. , Dierich Manfred P. 
Published: March 2007

AbstractMultinucleated giant cells (MGC), which are a common feature of various pathologic states, were generated in vitro by cytokine‐stimulation of human peripheral blood monocytes. As expected, conditioned medium, i.e. the supernatant of concanavalin A‐stimulated peripheral blood mononuclear cells, readily caused generation of MGC. Addition of a monoclonal antibody (mAb) against interferon‐γ (IFN‐γ) completely abrogated this effect. IFN‐γ alone, however, had a much smaller effect than the conditioned medium. All other cytokines tested [including interleukin (IL) 2, IL 4 and tumor necrosis factor‐α, which are known to activate monocytes] did not induce MGC nor did they enhance the effect of IFN‐δ.Formation of MGC could almost entirely be inhibited by mAb to the α or β chain of LFA‐1 and to a lesser extent by relatively high concentrations of a mAb against ICAM‐1, one of the ligands of LFA‐1. In contrast to the anti‐IFN‐γ mAb that had no significant effect on the formation of monocyte clusters, mAb against LFA‐1 inhibited clustering very efficiently.Antibodies directed to a number of different antigens present on the surface of monocytes (α chains of CR3 and CR4, HLA class I and II molecules, CD14 and CD16 antigens) had little or no effect on the generation of MGC. IFN‐γ, but not the concanavalin A‐induced supernatant clearly enhanced expression of LFA‐1 and ICAM‐1 on monocytes.The results indicate that cytokine‐induced generation of MGC is not possible without IFN‐γ, but most probably additional factor(s) enhance this effect. The mechanism(s) by which IFN‐γ promotes monocyte fusion apparently includes, among others, up‐regulation of LFA‐1 whose expression seems to be necessary but not sufficient for fusion.
Expression of complement alternative pathway proteins by endothelial cells. Differential regulation by interleukin 1 and glucocorticoids
Authors: Dauchel Hélène , Julen Nathalie , Lemercier Claudie , Daveau Maryvonne , Ozanne Denyse , Fontaine Marc , Ripoche Jean 
Published: March 2007

AbstractWe have studied the secretion of proteins of the alternative pathway of complement C3, factor B and factor H by human umbilical vein endothelial cells (HUVEC). Results showed that factor H and factor B are quantitatively secreted in abundance whereas C3 could only be detected when the cells are maintained in culture during long periods of time. Interferon‐γ stimulated factor H, factor B and, to a lesser extent, C3 secretions. Interleukin (IL) 1 had a differential effect on spontaneous C3, factor B and factor H secretions. In the presence of IL 1, there was a significant secretion of C3 occurring within a short period of culture. IL 1 also stimulated factor B secretion. There was a synergistic stimulating effect between IL 1 and interferon‐γ to bring C3 and factor B productions by HUVEC to very high levels. In contrast, factor H secretion was consistently inhibited by IL 1. Local increase in C3 and factor B secretions by endothelial cells in the presence of IL 1 may have important implications in the inflammatory reaction. In striking contrast, the glucocorticoid dexamethasone (DXM) had modulatory effects which are consistent with its anti‐inflammatory properties. DXM, at therapeutic concentrations, decreased C3 and factor B secretions and increased factor H secretion. Local modulation of complement protein secretion by DXM appears to be a new mechanism by which this glucocorticoid may control inflammation.