bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of FcγRIII defines distinct subpopulations of fetal liver B cell and myeloid precursors
Authors: Carlsson Leif , Candéias Serge , Staerz Uwe , Keller Gordon 
Published: March 2007

AbstractWe have isolated four distinct fetal liver (FL) populations based on the expression of AA4.1 and the low‐affinity Fcγ receptors type II and III (FcγRII/III), and characterized them with respect to B cell, T cell, and myeloid precursor content. Polymerase chain reaction analysis revealed that the prevalent FcγR isoform at this stage of FL development (day 12 of gestation) was FcγRIII. Two of the four populations, one which expressed AA4.1 but little if any FcγRII/III (AA4.1+), and one which expressed abundant levels of both markers (AA4.1+/ FcR+), contained B cell precursors that grew and differentiated to generate VHDJH‐rearranged B‐lineage cells on S‐17 stromal cells in the presence of IL‐7. When cultured on FLST2 stromal cells only the AA4.1+ cells generated VHDJH‐rearranged B‐lineage cells. T cell precursors as assayed by their ability to repopulate fetal thymi in organ culture were found only in the AA4.1+ fraction. In contrast to the lymphoid precursors, myeloid precursors able to generate colonies in methyl cellulose cultures were found in all four fractions including the one which expressed FcγRII/III but no AA4.1 (FcR+) and the one which expressed neither marker (AA4.1−/FcR−). The AA4.1+ population which contained both B cell and T cell precursors was enriched for precursors from many myeloid lineages including the most immature ones which generated multilineage colonies. In contrast, the AA4.1+/FcR+ population, which also contained B cell precursors, was almost devoid of myeloid precursors and the few that were detected were committed to the macrophage lineage. The population defined as FcR+ was also enriched for precursors; however, the majority of these were committed to the erythroid, the macrophage and the mast cell lineage. The fourth population which expressed neither marker (AA4.1−/FcR−) was enriched for relatively mature erythroid precursors which were not present in any of the other fractions. Together, these findings demonstrate that fractionation of FL cells on the basis of AA4.1 and FcγRII/III expression distinguishes subpopulations of B cell and myeloid precursors and suggests that the low‐affinity FcγRIII could play a role in the development of early hematopoietic cells at this stage of ontogeny.
Both allelic forms of the rat T cell differentiation marker RT6 display nicotinamide adenine dinucleotide (NAD)‐glycohydrolase activity, yet only RT6.2 is capable of automodification upon incubation with NAD
Authors: Haag Friedrich , Andresen Viola , Karsten Stefan , Koch‐Nolte Friedrich , Thiele Heinz‐Günter 
Published: March 2007

AbstractThe finding that recently cloned mono‐ADP‐ribosyltransferases show sequence similarity to the rat T cell differentiation marker RT6 has led us to investigate the enzymatic activity of this alloantigenic system. To search for ADP‐ribosylation of cell surface proteins, T cell populations from RT6.1‐ and RT6.2‐expressing rat strains, as well as RT6.1+ and RT6.2+T‐T hybridoma cell lines, were incubated with [32P]nicotinamide adenine dinucleotide (NAD). All RT6.2+, but no RT6.1+ or RT6− cells, show incorporation of radioactivity into a single protein which could be identified as RT6.2 by immunoprecipitation with monoclonal antibodies. This automodification of RT6.2 is covalent, requires intact NAD as substrate, and displays characteristics typical for linkage of ADP‐ribose to arginine. The alloantigens RT6.1 and RT6.2 differ in ten amino acids, RT6.2 having two arginine residues not present in RT6.1. Both alloantigens were found to display potent NAD‐glycohydrolase activity.
Transgenic mice expressing high levels of soluble TNF‐R1 fusion protein are protected from lethal septic shock and cerebral malaria, and are highly sensitive to Listeria monocytogenes and Leishmania major infections
Authors: Garcia Iréne , Miyazaki Yoshitaka , Araki Kimi , Araki Masatake , Lucas Ralf , Grau Georges E. , Milon Geneviéve , Belkaid Yasmine , Montixi Christine , Lesslauer Werner , Vassalli Pierre 
Published: March 2007

AbstractMice bearing a transgene coding for a soluble tumor necrosis factor receptor type 1 (TNFR1)‐FeIgG3 fusion protein and placed under the control of the alpha‐1‐antitrypsin gene promoter were generated. Depending on the mouse line, blood levels of the protein ranged from 25 ng/ml to over 100 μg/ml; this level of expression was most often transmitted to the transgene‐bearing progeny as a relatively stable feature. High‐expressor mice were completely resistant to lipopolysaccharide‐induced shock and lethality, including after D‐galactosamine sensitization, and mice expressing about 1 μg of the fusion protein/ml were partially (60%) protected. In contrast, mice expressing less than 0.1 μg of the protein/ml were more sensitive than controls with respect to incidence and time of death, even though the biological activity of serum tumor necrosis factor (TNF) was partially neutralized. High‐expressor mice of the adequate genetic background were markedly, although not completely, protected from death by cerebral malaria after injection with Plasmodium berghei. They were highly susceptible to Listeria monocytogenes, dying from bacterial dissemination after sublethal infection, and to Leishmania major, displaying severe, non‐healing lesions after local infection. Under the same conditions, mice expressing about 1 μg protein/ml were only partially sensitive to these last agents, compared to nontransgenic littermate mice which were fully resistant. These transgenic mice represent a model of permanent, complete or partial, impairment of TNF use, which compares favorably, for ease of breeding and for the range of effects, to mice bearing gene disruptions.
Apoptotic death of lymphocytes in murine acquired immunodeficiency syndrome: Involvement of Fas‐Fas ligand interaction
Authors: Kanagawa Osami , Vaupel Barbara A. , Korsmeyer Stanley J. , Russell John H. 
Published: March 2007

AbstractMurine acquired immunodeficiency syndrome (MAIDS) is caused by a defective murine leukemia virus. The disease is characterized by abnormal lymphoproliferation, impaired T and B cell function and aberrant regulation of cytokines. Both T and B lymphocytes show activated phenotypes, but undergo apoptotic death with characteristic DNA fragmentation. These results indicate the presence of a continuous activation death pathway of the lymphocytes in MAIDS. Overexpression of the bcl‐2 transgene in lymphocytes showed no effect on the apoptotic cell death or on the development of the disease. In contrast, mice carrying mutations in either Fas or Fas ligand exhibited accelerated progression of the disease upon infection with MAIDS virus. These results suggest the involvement of Fas‐Fas ligand system in the pathogenesis of MAIDS.
Thy‐1‐mediated activation of rat basophilic leukemia cells does not require co‐expression of the high‐affinity IgE receptor
Authors: Dráberová Lubica , Dráber Petr 
Published: March 2007

AbstractThe glycosylphosphatidylinositol (GPI)‐anchored protein Thy‐1 is one of the most abundant molecules expressed on the surface of rat mast cells and rat basophilic leukemia cells, RBL‐2H3. Antibody‐mediated aggregation of Thy‐1 induces in these cells release of secretory components; so does aggregation of the receptor with high affinity for IgE (FcϵRI). To examine whether there is any relationship between Thy‐1‐ and FcϵRI‐mediated activation, we have isolated from mutagenized RBL‐2H3 cells a variant cell line deficient in the expression of surface FcϵRI, and analyzed its ability to be activated by an antibody to Thy‐1. Northern and immuno‐blot analyses revealed that the variant cells were deficient in the expression of a structural or a regulatory gene for FcϵRI γ subunit. The cells did not respond by release of secretagogues and protein‐tyrosine phosphorylation to IgE and antigen and anti‐FcϵRI monoclonal antibody (mAb) but their response to anti‐Thy‐1.1 mAb and calcium ionophore A23187 was retained. Transfection of the cloned FcϵRI γ subunit into the variant cells restored the surface expression of FcϵRI and responsiveness to both the antigen and anti‐FcϵRI mAb but had no effect on responsiveness to anti‐Thy‐1 mAb. The combined data indicate that aggregation of surface Thy‐1 glycoproteins activates a metabolic pathway which is independent of the presence of FcϵRI γ subunit and surface expression of FcϵRI.
Molecular characterization of human CD94: A type II membrane glycoprotein related to the C‐type lectin superfamily
Authors: Chang Chiwen , Rodríguez Antonio , Carretero Marta , López‐Botet Miguel , Phillips Joseph H. , Lanier Lewis L. 
Published: March 2007

AbstractNatural killer (NK) cells preferentially express several genes of the C‐type lectin superfamily which have been implicated in the regulation of NK cell function. We demonstrate that CD94 is a type II membrane protein encoded by a unique gene of the C‐type lectin superfamily. While homology of CD94 with the NK cell‐associated NKR‐P1 and NKG2 C‐type lectin genes is limited to the structural motifs conserved in the carbohydrate recognition domain, all of these genes are on human chromosome 12, the syntenic of mouse chromosome 6, where genes of the NK complex (NKR‐P1 and Ly‐49) are located. An unexpected feature of CD94 is the essential absence of a cytoplasmic domain, implying that association with other receptors may be necessary for the function of this molecule.
CD4 and CD45 regulate qualitatively distinct patterns of calcium mobilization in individual CD4+ T cells
Authors: Leitenberg David , Constant Stephanie , Lu Dan Dan , Smith Brian R. , Bottomly Kim 
Published: March 2007

AbstractAn early consequence of T cell activation is an increase in intracellular calcium concentration. Recent advances in video laser microscopic techniques enable the examination of individual cells over time following stimulation. Such studies have revealed that cells can undergo qualitatively distinct patterns of calcium mobilization, suggesting that different patterns of calcium flux may be associated with different signaling pathways and may differentially affect late events in cell activation. In this report, we identify distinct patterns of calcium mobilization in CD4+ T cells following the antibody‐mediated cross‐linking of either CD3 or CD4, or following the cross‐linking of both CD3 and CD4 simultaneously. These effects can be further modified by the cross‐linking of CD45. We find that antibody cross‐linking of CD3 alone induces a single spike in the vast majority of cells shortly after the addition of the cross‐linking antibody. In contrast, cross‐linking CD4 alone induces a delayed pattern of repetitive calcium spikes which are decreased in amplitude compared to CD3 cross‐linking. Simultaneous cross‐linking of CD3 and CD4 induces a sustained increase in intracellular calcium mobilization which is dependent on the presence of extracellular calcium. This sustained increase in intracellular calcium concentration is also seen following physiologic cross‐linking of CD3 and CD4 after T cell interaction with specific antigen and antigen‐presenting cells. Finally, the simultaneous cross‐linking of CD45, CD3 and CD4 abrogates the sustained increase in calcium seen following CD3 and CD4 cross‐linking. These results suggest that the qualitative nature of T cell receptor signaling can be modulated by the molecular association of other signaling molecules, which may be part of the T cell receptor complex or not.
Macrophage‐T cell interaction in experimental visceral leishmaniasis: failure to express costimulatory molecules on Leishmania‐infected macrophages and its implication in the suppression of cell‐mediated immunity
Authors: Saha Bhaskar , Das Gobardhan , Vohra Harpreet , Ganguly Nirmal K. , Mishra Gyan C. 
Published: March 2007

AbstractThe most important immunopathological consequence of infection with Leishmania seen in murine and human hosts is the suppression of T cell‐mediated immune responses to both mitogens and leishmanial antigens. It has been suggested that this suppression is mediated by macrophages, either by defective antigen processing and presentation or by the elaboration of suppressive mediators like prostaglandins. Optimum activation of T helper cells requires not only T cell receptor occupancy by the antigen‐Ia complex, but also costimulatory signals provided by the antigen‐presenting cells. We investigated the status of several costimulatory molecules on infected macrophages from both genetically susceptible BALB/c and resistant C57BL/6 mice. Our results demonstrate that upon parasitization, the macrophages become unable to deliver costimulatory signals to T helper cells, and that this effects is mediated by prostaglandins, as the inhibition of its synthesis by indomethacin recovered the defect. Upon infection with L. donovani, B7‐1 expression was decreased, while ICAM‐1 was marginally increased in BALB/c macrophages and there was no significant change in the expression of B7‐1 and ICAM‐1 in Leishmania‐infected C57BL/6 macrophages. Expression of VCAM‐1 did not change during infection. This selective alteration in the expression of costimulatory molecules on L. donovani‐infected BALB/c macrophages was caused by the living parasite, as shown by the fact that killing of the parasites by stibogluconate led to no alteration in the levels of costimulatory molecules. We found that the change in B7‐1 expression on the surface of infected macrophages resulted in the inhibition of delayed‐type hypersensitivity‐mediating functions of T helper cells from BALB/c mice. The results described in this study not only throw light on the possible mechanism of leishmanial pathogenesis, but also open up the possibility of immunotherapy of leishmaniasis by selective manipulation of costimulatory molecules.
Various V‐J rearrangement efficiencies shape the mouse λ B cell repertoire
Authors: Boudinot Pierre , Rueff‐Juy Dominique , Drapier Anne‐Marie , Cazenave Pierre‐André , Sanchez Pierre 
Published: March 2007

AbstractThe diversity of the B cell repertoire of Cx knockout mice is limited by the expression of four λ light chain types. Among the spleen B cells, λ1 is expressed by the majority (58%) of cells, and λ3 by the minority (8%), while λ2(V2) and λ2(Vx) are expressed in intermediate quantities (18% and 16%, respectively). To assess the influence of mechanistic pressures on the λ subtype distribution, the proportions of the different λ rearrangements were determined in various B cell subpopulations divided on the basis of the λ subtype expressed, and the VλJλ junction sequences were studied at different steps of B cell differentiation (pre‐B, immature and mature B cells). The data show that (1) the ratio of productive/non‐productive VJ junctions is determined by the nature of the λ segments that are rearranged as can be observed in the pre‐B cells, (2) V1‐J1 non‐productive rearrangements are often found in the λ1‐negative B cells in the periphery, and (3) V1J3 junctions are often non‐productive regardless of the nature of the cells analyzed. Our results, therefore, suggest that a strong probability of initiating a V1‐J1 rearrangement and a weak probability of giving a productive V1J3 junction are responsible for the λ1 dominance and the λ3 under‐expression, respectively. The intermediate proportion of λ2(V2) subtype is most likely due to a probability of obtaining a productive joint that is better than that for V1J3 and a probability of initiating a rearrangement that is lower than that for V1J1. However, the λ2(Vx) cell proportion cannot be determined only by these parameters.
The majority of murine VH12‐expressing B cells are excluded from the peripheral repertoire in adults
Authors: Ye Jian , McCray Suzanne K. , Clarke Stephen H. 
Published: March 2007

AbstractWe have previously demonstrated that at birth most productive (P) VH12 rearrangements in B10.H‐2aH‐4bp/Wts (2a4b) mice encode a ten‐amino acid CDR3, and that a significant fraction of the expected repertoire is absent. We have now examined the adult VH12 CDR3 repertoire involving all four JH gene segments in both peritoneum and spleen. Of the 74 P VH12 rearrangements from these tissues 67 encode a CDR3 of ten amino acids and include a Gly in the fourth position (designated 10/G4). Most of these rearrangements appear to derive from phosphatidylcholine (PtC)‐specific B cells, which also have a 10/G4 VHCDR3, since few 10/G4 P rearrangements were present in spleen cells depleted of PtC‐specific B cells. Thus, the VH12 B cell repertoire in adult mice is largely restricted to the use of a single CDR3 motif and to a single antigen specificity. This bias results from two selection events: (1) selective exclusion of most VH12 B cells from the peripheral repertoire, and (2) clonal expansion in the periphery of VH12 B cells that have a 10/G4 VHCDR3 and bind PtC. Analysis of VH12‐JH1 rearrangements in viable motheaten (mevJmev) mice, which have an abnormal B cell repertoire due to a defective phosphatase (Hcph) and have barely detectable numbers of PtC‐specific B cells, indicates that selective exclusion of VH12 B cells from the peripheral repertoire occurs normally, but that clonal expansion of 10/G4 VH12 B cells is minimal. This is evidence that the selective exclusion of VH12 B cells from the peripheral repertoire and the clonal expansion of VH12 B cells with a 10/G4 CDR3 are due to independent signaling events.
Intercellular adhesion molecule‐3 is the predominant co‐stimulatory ligand for leukocyte function antigen‐1 on human blood dendritic cells
Authors: Starling Gary C. , McLellan Alexander D. , Egner William , Sorg Rüdiger V. , Fawcett Jonathan , Simmons David L. , Hart Derek N. J. 
Published: March 2007

AbstractDendritic cells (DC) are potent stimulators of primary T lymphocyte responses to foreign antigen. The initial DC‐T lymphocyte interaction involves the binding of the adhesion molecule leukocyte function antigen‐1 (LFA‐1; CD11a/CD18) on the T lymphocyte to an intercellular adhesion molecule (ICAM) on the DC. Although blood and tonsil DC express ICAM‐1 (CD54) and ICAM‐2 (CD102) on their surface, anti‐ICAM‐1 and anti‐ICAM‐2 monoclonal antibodies (mAb) have little inhibitory activity on the DC‐stimulated mixed leukocyte reaction (MLR). We therefore examined the expression of the more recently identified LFA‐1 ligand, ICAM‐3 (CD50), in comparison to ICAM‐1 and ICAM‐2 on blood DC and sought a functional role for ICAM‐3 in DC‐mediated T lymphocyte responses. Resting blood DC expressed significantly more ICAM‐3 than ICAM‐1 or ICAM‐2 as assessed by flow cytometry. Treatment of resting DC with interferon‐γ led to increased expression of ICAM‐1; however, ICAM‐2 and ICAM‐3 levels remained relatively constant. Solid‐phase recombinant chimeric molecules ICAM‐1‐, ICAM‐2‐ and ICAM‐3‐Fc were able to co‐stimulate CD4+T lymphocyte proliferation in conjunction with suboptimal solid‐phase CD3 mAb 64.1. However, the anti‐ICAM‐3 mAb CAL 3.10 inhibited a DC‐stimulated MLR to a greater extent than anti‐ICAM‐1 or anti‐ICAM‐2 reagents and appeared to act by blocking the DC ICAM‐3‐ T lymphocyte LFA‐1 interaction. As ICAM‐3 is the predominant LFA‐1 ligand on resting blood DC, we postulate that DC may utilize ICAM‐3 for initial DC‐T lymphocyte interactions, and that ICAM‐1, which is up‐regulated upon DC activation, and/or ICAM‐2, may contribute to DC migration or later phases of the T lymphocyte activation process.
Stimulation of a memory B cell response does not require primed helper T cells
Authors: Leclerc Claude , Sedlik Christine , Lo‐Man Richard , Charlot Bernadette , Rojas Marie , Dériaud Edith 
Published: March 2007

AbstractThe use of universally immunogenic T cell epitopes, such as those identified in tetanus toxin or malaria circumsporozoite protein, could represent a major improvement in the development of synthetic vaccines. However, one limitation of this approach is the lack of T cell cross‐reactivity between the vaccine and the pathogen. To determine whether the memory B cell response elicited by immunization with a synthetic peptide containing a B cell epitope linked to a T cell epitope can be restimulated by the same B cell epitope linked to different T cell epitope(s), we used a synthetic peptide which contains non‐overlapping B and T cell determinants from hepatitis B surface antigen (HBsAg) of hepatitis B virus (HBV). The results of this study clearly show that primed T cells can increase the antibody response against a B cell epitope linked to the priming T cell determinant. However, the antibody response obtained was weaker than that obtained after two injections of the peptide containing both B and T cell epitopes, showing the important role played by memory B cells in secondary antibody responses. Moreover, a strong antibody response against the B cell epitope was elicited by boosting mice with the B cell epitope linked to a heterologous carrier, thus demonstrating that a strong B cell memory response can be revealed in the absence of primed T cells. These results therefore provide new important information for the design of synthetic or recombinant vaccines.
CD8+ Type 1 CD44hi CD45 RBlo T lymphocytes control intracellular Brucella abortus infection as demonstrated in major histocompatibility complex class I‐ and class II‐deficient mice
Authors: Oliveira Sergio C. , Splitter Gary A. 
Published: March 2007

AbstractGenetically engineered mice with a targeted disruption in the β2‐microglobulin (β2‐m) gene or the H2‐I‐Aβ chain (αβ) which lack functional CD8+ or CD4+ T cells, respectively, were used to assess the role of T cell subsets in Brucella abortus infection. Murine brucellosis was markedly exacerbated in β2‐m‐deficient mice (β2‐m−/−) compared to Aβ mutant (Aβ−/−) or C57BL/6 mice, strongly indicating that optimal resistance to B. abortus requires CD8+ T cells. Splenocytes from Brucella‐primed β2‐m−/−, αβ−/− and C57BL/6 mice exhibited a type 1 cytokine profile marked by elevated IFN‐γ mRNA expression and protein production, and basal levels of IL‐2 and IL‐4 transcripts. B. abortus did not induce secretion of TGF‐β1, but substantial IL‐10 activity was detected in spleen cell supernatants from all mouse strains studied. CD8+ T cells from Aβ−/− and C57BL/6 mice displayed a CD44hi CD45RBlo phenotype and a type 1 cytokine transcription profile featuring high levels of IFN‐γ mRNA. Additionally, we have shown the ability of C57BL/6 CD8+ CTL to kill Brucella‐infected macrophages. This study illustrates the predominant role of MHC class I‐restricted T cells in controlling B. abortus infection.