bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin 4 and soluble CD23 as progression factors for human B lymphocytes: analysis of their interactions with agonists of the phosphoinositide “dual pathway” of signalling
Authors: Gordon John , Cairns Jennifer A. , Millsum Michelle J. , Gillis Steven , Guy Graeme R. 
Published: March 2007

AbstractHuman B lymphocytes pre‐activated for 24 h with a combination of phorbol dibutyrate [P(BU)2] and ionomycin were found to provide excellent targets for assessing the detailed action of B cell progression factors. Both recombinant interleukin 4 (IL4) and affinity‐purified 25‐kDa fragment of the CD23 molecule (sol‐CD23) were shown to be active in this assay. While the progression activity of IL4 was enhanced by continued co‐culture with P(Bu)2, that of sol‐CD23 was found to be more strictly dependent upon such a joint application with the phorbol ester. Similar requirements were observed for triggering cell‐cycle progression in the pre‐activated B cells when using a stimulating CD23 antibody. Ionomycin, in contrast to P(BU)2, did not augment either IL4 or sol‐CD23 in these assays but did enhance significantly the progression activity of an anti‐CDw40 antibody. When added to B cells concomitantly with, or prior to, a high dose of phorbol ester, IL 4 unexpectedly down‐regulated the subsequent mitogenic response to this agent whereas, when added 24 h later, IL4 up‐regulated such stimulations. The latter sequence of additions resulted in a particularly dramatic induction of CD23 at the B cell surface, much more so than seen when B cells were incubated with either IL4 alone or with IL 4 and P(Bu)2 together. This up‐regulation of surface CD23 was, in turn, mirrored by the appearance of large amounts of the soluble form of the molecule in such cultures. The findings are discussed with reference to possible mechanisms through which IL 4 and CD23 interact to exert their multiple actions on B cell regulatory pathways.
Physiology of murine B lymphocytes I. Life‐spans of anti‐m̀ and haptenated Ficoll (thymus‐independent antigen)‐reactive B cells
Authors: Udhayakumar Venkatachalam , Niranjan Gouda S. , Subbarao Bondada 
Published: March 2007

AbstractWe have evaluated the life‐span of B lymphocytes by measuring the functional reactivity of normal B cells upon transfer into xid mice, which do not respond to anti‐μ, fluoresceinated‐Ficoll (FL‐Ficoll) and 2,4,6‐trinitrophenyl aminoethylcarbamylmethyl Ficoll (TNP‐Ficoll). After 4 days of transfer only 30–40% of anti‐μ‐reactive cells decayed leaving behind 60–70% of B cells which appeared to decay slowly. Even 10 days after transfer ˜ 40% of anti‐γ‐reactive B cells can be recovered from the recipients. This result demonstrates the existence of heterogeneity in the life‐spans of anti‐μ‐reactive B lymphocytes and that a major population (60–70%) of B cells persists beyond 4 days. Interestingly, the short‐lived B cell subpopulation was not detected when the decay of the antigen‐specific B cells was studied. Thus, TNP‐Ficoll and FL‐Ficoll‐reactive B cells were found to be long lived and such B cells did not decline at all, even 5 months after transfer into xid mice.
A single cDNA encodes multiple Ly‐6 antigenic specificities
Authors: Korty Patricia E. , Cohen David I. , Shevach Ethan M. 
Published: March 2007

AbstractTo determine the relationship between the structure and function of proteins coded for by the Ly‐6 gene complex, we have transfected a cDNA for a Ly‐6.2 specificity into COS‐7 cells. A number of monoclonal antibodies which have been shown to be capable of inducing T cell activation and which have been previously considered to recognize distinct proteins all reacted with the same transfected gene product. The approach used in these studies should be useful to further elucidate the complexities of the Ly‐6 alloantigen system.
Interleukin 2 and low molecular weight B cell growth factor are T cell‐replacing factors for different subpopulations of human B cells*
Authors: Callard Robin E. , Smith Susan H. 
Published: March 2007

AbstractBoth recombinant human interleukin 2 (rhIL2) and low molecular weight B cell growth factor (BCGFlow) were shown to be T cell‐replacing factors (TRF) in specific antibody responses to influenza virus by human blood and tonsillar B cells. When B cells were separated into high and low‐density populations on Percoll gradients at 1.074 kg/l, IL2 was found to act as a TRF only on the low‐density B cells, whereas BCGFlow was a TRF for high‐density B cells with a lesser effect on low‐density B cells. Both populations of B cells responded well in the presence of T cells. The high‐density B cells could not be activated to respond to IL2 by either IL1, rhIL4 or by a CD22 monoclonal antibody known to enhance B cell activation. In contrast, a 24‐h preincubation with T cells and antigen appeared to prime high‐density B cells to respond to IL2. These results show that high‐density B cells can in fact respond to TRF, and that IL2 and BCGFlow, act on different populations of B cells which may be defined by prior exposure to T cells.
Cloned CD3+ TcRα/β− TiγA− peripheral blood lymphocytes compared to the Ti γA+ counterparts: structural differences of the γ/δ receptor and functional heterogeneity
Authors: Jitsukawa Setsuko , Triebel Frédéric , Faure Florence , And Christine Miossec , Hercend Thierry 
Published: March 2007

AbstractWe have assessed the organization of T cell γ rearranging genes (TRG) in circulating TcRγ/δ+ lymphocytes which do not express Vγ9‐encoded TiγA+ γ chain. Following purification of the minor TcRγ/δ+ TiγA− fraction, cloned cell lines were developed from peripheral blood of 5 individuals. Out of the 26 clones studied, only 3 TcRγ/δ+ TiγA‐ cells were found to express a disulfide‐linked C1‐encoded γ chain. The remaining 23 TiγA− clones with a C2‐encoded nondisulfide‐linked receptor were found to display rearrangements of various V genes to 52 segments on both chromosomes; there was no predominance of a unique rearrangement even though the TRG‐V3 and ‐V4 genes belonging to subgroup I were frequently employed. Together, these findings further strengthen the hypothesis that lymphocytes with a Cγ1 encoded chain are produced earlier in T cell ontogeny than the Cγ2 counterparts. The “non‐major histocompatibility complex (MHC) requiring” (i.e., “natural killer‐like”) cytotoxicity mediated by many TcRγ/δ+ TiγA− cells appeared to be very low as compared to that of Ti γA+ clones. Yet, treatment by the OKT3 monoclonal antibody revealed a strong lytic potential in the TiγA− lymphocytes with little, if any, natural killer‐like activity. Thus, with respect to the latter function, a substantial heterogeneity is found in cells expressing distinct γ chains. In an attempt to characterize undefined specificities of TiγA− lymphocytes, they were screened against a panel of Epstein‐Barr virus‐transformed B cell lines homozygous for HLA‐DR1 to DR10 determinants; one of the clones was found to recognize DR7. In light of reports from other groups describing class I‐related specificities, it is apparent that TcRγ/δ+ lymphocytes are able, like the TcRα/β+, to recognize and kill target cells through either an MHC‐dependent (with involvement of either class I or class II gene products) or a non‐MHC‐requiring pathway.
Towards an idiotype vaccine against mammary tumors. Induction of an immune response to breast cancer‐associated antigens by anti‐idiotypic antibodies
Authors: Smorodinsky Nechama Ina , Ghendler Yoseph , Bakimer Ronit , Chaitchuk Samario , Keydar Iafa , Shoenfeld Yehuda 
Published: March 2007

AbstractPreviously we have reported on the production of two sets of human monoclonal antibodies reacting with mouse mammary tumor virus (MMTV) and human mammary tumor virus (HuMTV) cross‐reacting antigens. B11 is a monoclonal IgG generated by the human‐human hybridoma technique using axillary lymph node of breast cancer patients. 4.616 is a monoclonal IgG established by the mouse‐human hybridoma procedure using peripheral blood lymphocytes of a healthy investigator working with the breast cancer cell line T47D which secretes HuMTV antigens. Two anti‐idiotypic (Id) antibodies were produced by immunizing rabbits with B11 or 4.616. Following exhaustive adsorption on unrelated human‐Ig, fetal calf serum and purification on B11 or 4.616 affinity columns, the anti‐Id antibodies were shown to react specifically with their respective Id. The binding of these anti‐Id antibodies to the respective Id was specifically inhibited by prior incubation of the Id with MMTV and/ or HuMTV antigensRabbit anti‐B11 and rabbit anti‐4.6/6 anti‐Id antibodies were employed to immunize female C3Heb mice. Following immunizations, humoral and cellular immune responses to MMTV‐related antigens could be demonstrated. The sera of the mice contained anti‐MMTV antibodies and delayed‐type hypersensitivity was specifically expressed when irradiated cells of the Mm5MT line (which carry surface MMTV antigens) were injectedOur results support the notion that anti‐Id antibodies harboring the internal image can immunize animals against tumor cells bearing on their surface viral‐associated antigens.
Cooperative effect of interferon‐γ and tumor necrosis factor‐α on the induction of the class II antigen‐associated invariant chain expression
Authors: Pessara Ulrich , Momburg Frank , Koch Norbert 
Published: March 2007

AbstractThe regulation of the invariant chain (Ii) expression was studied in the human colon carcinoma cell line HT‐29 that constitutively expressed neither Ii nor class II antigens. Upon stimulation of HT‐29 cells with a combination of human recombinant tumor necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ), expression of mRNA and protein of the invariant chain were induced. In contrast, administration of TNF‐α or IFN‐γ alone had no effect. A delayed induction of Ii mRNA, which was first detected 10–12 h after stimulation, was observed; this suggests an indirect regulatory mechanism. Stimulation with both IFN‐γ and TNF‐α led to the co‐expression of class II antigens with the invariant chain. In order to study the genetic basis for this stimulation the murine invariant chain gene (800 bp 5′ flanking sequences and the structural gene) was transfected into HT‐29 cells and transfected cells were tested for the ability to respond to IFN‐γ and TNF‐α. Simultaneous application of both cytokines had a strong effect on the induction of the murine invariant chain. IFN‐γ alone had no effect and TNF‐α only marginally stimulates murine invariant chain expression. The transfection experiment indicates that the murine invariant chain gene construct contains the structural elements which are responsible for regulation with IFN‐γ and TNF‐α. We determined whether the cooperative effect of TNF‐α and IFNγ is also found in vivo. Stimulations of mice were performed with TNF‐α, IFN‐γ and a combination of both. The immunohistological analysis of kidney tissue sections revealed that TNF‐α had no effect on Ii and Ia expression. Upon IFN‐Y treatment a minor subset of renal tubules showed staining for Ii, and less prominently also for Ia. However, simultaneous application of both cytokines led a strong induction of both Ii and Ia antigens in renal epithelial cells, thus suggesting that this synergistic effect potentially occurs under physiological conditions.
Clonal analysis of human T cell activation by the Mycoplasma arthritidis mitogen (MAS)
Authors: Matthes Michaela , Schrezenmeier Hubert , Homfeld JÖRg , Fleischer Sabine , Malissen Bernard , Kirchner Holger , Fleischer Bernhard 
Published: March 2007

AbstractMycoplasma arthritidis produces an as yet undefined soluble molecule (MAS) that has a potent mitogenic effect on T cells of several species. We have used cloned human cytotoxic and proliferative T lymphocytes to dissect the molecular mechanism of T cell activation by this mitogen. Reactivity to MAS is clonally expressed among T cell receptor (TcR) α/β chain‐expressing T cell clones of CD4+ or CD8+ phenotype, as well as CD4−8− TcRα/β chain‐negative T lymphocyte clones expressing the CD3‐associated TcRγ chain. MAS is able to induce cytotoxicity and/or proliferation in these T cell clones. For triggering of these T cells, regardless of their phenotype of specificity, the presence of autologous, allogeneic or xenogeneic major histocompatibility complex (MHC) class II molecules on accessory cells or target cells is necessary. However, T cells do not immunologically recognize MAS on class II molecules, since a direct action of MAS on the T cells themselves can be demonstrated. Triggering of T cells by MAS can be blocked by monoclonal antibodies against CD2, CD3 and the TcRα/β chain dimer. We discuss as a possible explanation that MAS is a functionally bivalent molecule cross‐linking TcR and MHC class I1 molecules. Thus, the mechanism of T cell activation by MAS has striking similarities to the mechanisms by which Staphylococcal enterotoxins activate T cells. It is intriguing that a similar mitogenic principle has been developed by two evolutionary distinct pathogenic microorganisms.
Functional interaction between B cell subpopulations defined by CD23 expression
Authors: Armitage Richard J. , Goff Lindsey K. 
Published: March 2007

AbstractUsing the CD23 monoclonal antibody (mAb) MHM6 and sheep anti‐mouse Ig bound to magnetic beads we have obtained highly purified populations of MHM6+ and MHM6− tonsil B cells. We have found that the increased expression of MHM6 reactivity seen on B cells after activation results from up‐regulation of antigen on cells already weakly positive and not from expression of new antigen on the previously negative population. The strong proliferative responses of MHM6+ cells seen in the presence of anti‐IgM (αμ) and interleukin 4 (IL4) or the CDw40 mAb G28‐5, and with Staphylococcus aureus Cowan I (SAC), and to a lesser extent with the phorbol ester 12‐0‐tetradecanoylphorbol 13‐acetate (TPA), resemble that seen among unfractionated B cells. In contrast, the MHM6− population cultured alone responds only weakly to αμ+ G28‐5 or SAC and exhibits virtually no response to αμ + IL4 or TPAWith all these mitogenic stimuli, tritiated thymidine uptake by the MHM6− population is augmented three‐ to sixfold by the addition of mitomycin C (MC)‐treated MHM6+ cells. Pretreatment of cells with anti‐leukocyte functional antigen 1 mAb has little effect on the subsequent proliferation of the MHM6− population but shows cell contact to be critical for the proliferation of MHM6′ cells. Such pretreatment has revealed that the functional interaction observed between MHM6+ and MHM6− cells is dependent on both cell contact and the presence of an MHM6+ cell‐derived soluble componentWe have found that addition of soluble CD23, purified from Epstein‐Barr virus‐transformed lymphoblastoid cell line supernatant, increases the proliferative response of MHM6− tonsil B cells to mitogenic stimuli in the presence of inactivated MHM6+ cells but has no effect on proliferation when MHM6+ cells are absentBy way of contrast to normal B lymphocytes, we have examined functional responses of prolymphocytic leukemia (PLL) B cells. Although these cells, when freshly isolated, show comparable levels of CD23 expression to normal B cells, this expression is not increased upon activation. In addition, in contrast to normal B cells, the PLL MHM6− population cultured alone shows a strong proliferative response to various mitogenic stimuli, comparable to that of MHM6+ or unfractionated cells, and this response is not augmented by the addition of MC‐treated MHM6+ cells. Thus, a novel functional interaction is described between normal, but not leukemic, B cell populations defined by their expression of CD23. This interaction involves two components, one mediated through cell contact and the other by the presence of soluble factor(s) derived from the MHM6+ cells with neither component alone being effective.
B lymphopoiesis on stromal cell clone: stromal cell clones acting on different stages of B cell differentiation*
Authors: Nishikawa Shin‐Ichi , Ogawa Minetaro , Nishikawa Satomi , Kunisada Takahiro , Kodama Hiroaki 
Published: March 2007

AbstractB lymphopoiesis supporting activities of two stromal cell clones, MC3T3‐G2/PA6 (PA6) and ST2, were compared. When normal bone marrow cells were cultured in these clones under Whitlock‐Witte‐type condition, mature B cells were generated only in the culture with the ST2 layer. The cells maintained on the PA6 layer, however, contained the precursor cells giving rise to mature B cells when transferred to the ST2 layer. Thus, PA6 is a stromal cell clone capable of supporting the early B progenitors but cannot support a further maturation step into pre‐B cells. The immunoglobulin heavy chain gene configuration of B progenitors maintained on the PA6 layer diversified after their transfer onto ST2 layer. This suggests that they are actually the earliest progenitors. This marked difference in the stromal cell activities between PA6 and ST2 could also be distinguished by stromal cell‐dependent pre‐B cell lines. Among four ST2‐dependent pre‐B cell lines tested, two grew only on the ST2 layer, which is capable of supporting B lymphopoiesis, while the others grew both on the ST2 and PA6 layers. These results strongly suggest that the process of intra‐marrow B cell development is controlled by more than one signal acting on different stages of B cell differentiation.
Immune responses to an adjuvant‐free native syngeneic myeloma protein (M315)
Authors: Kristoffersen Gunn , Hannestad Kristian 
Published: March 2007

AbstractMyeloma protein 315 (M315; isotype IgA, λ2) is used in this report as a model to explore the immunogenicity of a syngeneic Ig under nearly physiological conditions. We have previously shown that a synthetic peptide spanning the mutated HV3 loop of the L‐315 chain, when emulsified in complete Freund's adjuvant, elicits T helper cells (Th) that respond to a boost with L‐315 or M315, indicating that M315 is recognized as a processed protein antigen. We now show that the adjuvant‐free 7 S monomer of native or of mildly reduced and alkylated M315, given in divided doses totalling 300 or 800 μg to BALB/c mice, induced persistent anti‐M315 antibodies (Ab), a large part of which was IgG1 directed mainly to idiotypes (Id) associated with M315′s haptenbinding site. Polymers of M315 IgA (800 μg) failed to induce Ab, due probably to their rapid clearance into bile. Short‐term treatment with anti‐CD4 monoclonal Ab GK1.5 at the time of priming with 7s M315 inhibited the responses almost completely. The spleens of M315‐immune mice contained Th that recognized the L‐chain subunit of M315 as a carrier indicating that these Th did not require an assembled (VH‐VL) pair of 315 V regions to be activated. We also observed low amounts of Ab specific for epitopes of the Cα region. This evidence opens the possibility that a distinct autoimmune pathway exists for elicitation of rheumatoid factor (RF; auto Ab to Fcγ) that involves help to RF‐producing B cells by Id‐specific Th. We suggest that these Th recognize V‐region peptides from IgG that have been captured, processed and presented by these B cells.
Excessive production of interleukin 6/B cell stimulatory factor‐2 in rheumatoid arthritis
Authors: Hirano Toshio , Matsuda Tadashi , Turner Martin , Miyasaka Nobuyuki , Buchan Glenn , Tang Bo , Sato Kazuto , Shimi Masatoshi , Maid Ravinder , Feldmann Marc , Kishimoto Tadamitsu 
Published: March 2007

AbstractHigh levels of interleukin 6 (IL 6/B cell stimulatory factor‐2) were detected in synovial fluids from the joints of patients with active rheumatoid arthritis (RA). The cells found in freshly isolated synovial fluid constitutively expressed IL6 mRNA. The synovial tissues obtained by joint biopsy were also found to produce IL6 in vitro. Immunohistochemical analysis demonstrated that CD2+ T cells as well as CD20+ blastoid B cells in the synovial tissues produce IL6. The data indicate that IL6 is generated constitutively in RA and its overproduction may explain the local as well as the generalized symptoms of RA, since IL6 can function as B cell growth and differentiation factor as well as hepatocyte‐stimulating factor.
Decreased TcR‐CD3+ T cell numbers in healthy aged humans. Evidence that T cell defects are masked by a reciprocal increase of TcR‐CD3−CD2+ natural killer cells
Authors: Alés‐Martínez JoséE. , Alvarez‐Mon Melchor , Merino Francisco , Bonilla FéLix , Martínez‐A Carlos , Durántez Alberto , De La Hera Antonio 
Published: March 2007

AbstractWhile there is accumulating evidence to indicate the presence of functional abnormalities in T cells from aged healthy humans, their cellular basis remains unclear. By using two‐color immunofluorescence and multiparameter flow cytometry we show that (a) the number of peripheral blood antigen receptor‐positive (TcR‐CD3+) T cells is significantly lower in aged than in young adults; (b) the numbers of E‐rosette‐forming (CD2+) cells are maintained in the elderly due to a reciprocal increase in the frequency of TcR‐CD3− cells, which constitute only a minor lymphocyte subpopulation in young adults, and (c) TcR‐CD3−CD2+5− lymphocytes exhibit the phenotypic features of natural killer (NK) cells. By using functional assays we show the TcR‐CD3−CD2+16+ lymphocytes are indeed NK cells because they are activated by and lyse NK targets. In contrast, they are unresponsive to either phytohemagglutinin or mitogenic CD2 monoclonal antibody stimulation, which in turn activates TcR‐CD3+CD2+16− T cells. We conclude that the increase in TcR‐CD3−CD2+ NK cells masks the T cell reduction in aged humans by normalizing CD2+ cell frequencies. However, NK cells cannot functionally substitute the thymus‐derived lymphocytes they replace.
B cell precursors in chick embryos surgically bursectomized at 72 h of incubation
Authors: Lassila Olli , Alanen Anna , Vainio Olli , Houssaine Elisabeth , Pink J. Richard L. , Weber Wilfried T. 
Published: March 2007

AbstractTo determine the presence of precursor B cells in chick embryos surgically bursectomized at 72 h of incubation (E‐Bx) we studied chick chimeras that were produced by establishing parabiotic connections between blood vessels of chorioallantoic membranes of normal and surgically bursectomized chick embryos. Using sex chromosomes and a B cell alloantigen (Bu‐1a) as markers we showed that chick embryos bursectomized at 72 h of incubation contain B cell precursors capable of colonizing the bursa of Fabricius and developing into B lymphocytes. The repopulation capacity of 14‐day‐old embryonic spleen cells from E‐Bx recipients was tested by transferring them into age‐matched X‐irradiated Bu‐1‐disparate embryos. The results show that B cell precursors are present in 14‐day spleen of chick embryos bursectomized at 72 h of incubation. These precursors carry the Bu‐1 B cell alloantigen, suggesting that commitment to the B cell lineage can take place in the absence of bursa.
Identification of anti‐acetylcholinesterase and anti‐idiotype antibodies in human and experimental Chagas+ disease: pathological implications
Authors: Ouaissi Ali , Cornette Jocelyne , And Phillipe Velge , Capron Andre 
Published: March 2007

AbstractThis report presents evidence that human acetylcholinesterase (AChE; acetylcholine hydrolase, EC 3.1.1.7) exhibits immunological cross‐reactivity with the protozoan parasite Trypanosoma cruzi. The immunological probes used indicate that the cross‐reactive determinant is an oligosaccharidic epitope. Antibodies to AChE were detected in a high proportion of T. cruzi‐infected patients sera and during the experimental infection of BALB/c mice. Moreover, anti‐idiotypic antibodies against an anti‐AChE rabbit antibody or a monoclonal antibody to a parasite surface antigen of 80–85 kDa were detected in sera of patients presenting the chronic cardiac form of the disease. The antibodies were less frequently found in sera from individuals with asymptomatic chronic infection. Our data may provide a biochemical basis for denervation hypersensitivity in Chagas' disease. In addition, it may support the notion of an idiotype‐anti‐idiotype regulation of conducting tissue damage during the course of T. cruzi infection.