bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic and genetic characterization of a unique B lymphocyte deficiency in strain A/WySnJ mice
Authors: Miller David J. , Hayes Colleen E. 
Published: March 2007

AbstractThe elucidation of B lymphocyte development has been partially achieved through genetic models such as the X‐linked immunodeficiency (xid) mutation. We discovered a unique B lymphocyte developmental defect in strain A/WySnJ mice. We used single‐ and two‐color flow cytometry to analyze lymphocytes from A/J and A/WySnJ mice. Adult A/WySnJ mice had a severe B cell deficiency, which was apparent in the spleen, lymph nodes, peritoneum and peripheral blood, compared to adult A/J mice. An ontogeny study revealed that a developmental defect, inhibiting B lymphocyte maturation or differentiation but not B lymphopoiesis, was responsible for the deficiency. This maturational defect blocked the production of B220hi/Iahi/surface IgMlo B cells, and was manifested in the adult bone marrow and neonatal spleen, but not the adult spleen. Neither Ly‐1 B cells nor peripheral T cells were apparently affected by the A/WySnJ defect. The B cell immunodeficiency segregated as an autosomal co‐dominant trait in F1 and F2 mice. We propose that A/WySnJ mice have a novel genetic defect arresting B cell differentiation in adult bone marrow and neonatal spleen.
Anti‐α/β T cell receptor monoclonal antibody provides an efficient therapy for autoimmune diabetes in nonobese diabetic (NOD) mice
Authors: Sempé Pascal , Bédossa Pierre , Richard Marie‐Francoise , Villà Maria‐Carme , Bach Jean‐Francois , Boitard Christian 
Published: March 2007

AbstractThe nonobese diabetic (NOD) mouse is a relevant model for studying human insulin‐dependent diabetes mellitus (IDDM). The selective destruction of insulin‐secreting cells in this model is subsequent to an autoimmune reaction directed towards the β cells inside the islets of L angerhans of the pancreas. Given the key role played by T cells in the development of IDDM, we investigated a model of IDDM prevention in NOD mice by administration of a monoclonal antibody to the α/β dimer of the T cell receptor for antigen. Our data provide evidence that aiming at the T cell receptor protects against both spontaneous and cyclophosphamide‐induced diabetes in the NOD mouse. Interestingly, potencial clinical application is suggested by the efficient and durable reversal of recent onset diabetes in mice treated with anti‐α/β monoclonal antibody within 1 week following the clinical discovery of IDDM.
Major histocompatibility complex binding and T cell recognition of a viral nonapeptide containing a minimal tetrapeptide
Authors: Schulz Manfred , Aichele Peter , Schneider Reto , Hansen Ted H. , Zinkernagel Rolf M. , Hengartner Hans 
Published: March 2007

AbstractThe primary immune response of cytotoxic T lymphocytes in H‐2d and H‐2q mice to infection with lymphocytic choriomeningitis virus is directed mostly towards the common major T cell epitope of amino acids 112–132 on the viral nucleoprotein (NP). The molecules responsible for presentation of the T cell epitope NP112‐132 are in both haplotypes the MHC class I L antigens (Ld, Lq). Truncations of the amino and carboxy termini of the NP 112–132 sequence revealed the nonapeptide RPQASGVYM (NP118‐126) as a most effective peptide antigen, but even the tetrapeptide GVYM was recognized by CTL of both haplotypes in a class I antigen‐restricted specificity. When tyrosine (Y) or methionine (M) were substituted with alanine, CTL recognition of the altered nonamer required 106 to 108 times higher peptide concentrations and in one case (Y → A on Ld) the peptide was not recognized at all. Up‐modulation of the expression of Ld and Lq class I antigens as measured by flow cytometry correlated with the ability to present the peptide antigens. The only exception was peptide NP118‐126 (M → A), which was recognized by T cells on L‐Ld and L‐Lq target cells but failed to up‐regulate Ld and Lq antigens.
Molecular cloning of rat interleukin 4 cDNA and analysis of the cytokine repertoire of subsets of CD4+ T cells
Authors: McKnight Andrew J. , Barclay A. Neil , Mason Don W. 
Published: March 2007

AbstractRat peripheral CD4+ T cells may be subdivided into two functionally distinct subpopulations (OX‐22highCD4+ and OX‐22lowCD4+) on the basis of their reactivity with the monoclonal antibody MRCOX‐22, which recognizes a restricted epitope on the leukocyte common antigen (LCA, CD45). Previous studies have demonstrated the increased activity of the OX‐22highCD4+ subset in assays of cell‐mediated reactivity, whereas the reciprocal OX‐22lowCD4+ subset provides the majority of help for B cells in secondary antibody responses. Analyses of in vivo function have subsequently shown that the autoreactive activity associated with the OX‐22highCD4+ subset can be inhibited through a suppressor activity within the OX‐22lowCD4+ subset, indicating a further immunoregulatory role for these cells. Since the differential production of lymphokines such as interferon‐γ (IFN‐γ) and interleukin 4 (IL4) is believed to regulate alternative effector responses to a particular antigen, we have compared the lymphokine mRNA profiles of activated OX‐22highCD4+ and OX‐22lowCD4+ subsets using nucleic acid probes specific for rat IL 2, IFN‐γ and IL4, the latter of which has been isolated by a polymerase chain reaction cloning technique and its sequence is described. A higher frequency of cells expressed IL 2 mRNA in the OX‐22high subset, in accordance with the relative levels of IL 2 protein produced. In contrast, more IFN‐γ mRNA was detected in the OX‐22lowCD4+ subset 24 h after mitogenic stimulation although these cells have consistently been shown to produce less IFN‐γ protein than the OX‐22highCD4+ subset. This apparent paradox was resolved by the finding that the IFN‐γ mRNA levels in the OX‐22lowCD4+ subset declined rapidly after 24 h while the levels continued to rise in the OX‐22highCD4+ population such that at 48 h the relative levels were reversed. We have also demonstrated a higher level of IL 4 mRNA expression within the OX‐22lowCD4+ subset, which is undoubtably involved in the increased B cell helper activity mediated by this subpopulation and may be responsible, in part, for their active suppression of cell‐mediated immune responses.
A myeloma M104E private idiotope is represented predominantly among anti‐dextran, peritoneal cavity Ly‐1 precursor B cells
Authors: Lehmann Hans‐Peter , Lehle Georg 
Published: March 2007

AbstractPublic and private idiotopes (Id) had been defined in the BALB/c anti‐dextran B1355 fraction S (Dex) response by means of syngeneic monoclonal anti‐M 104E Id antibodies. Most of the primary anti‐Dex antibodies shared the public Id‐1 while the private Id‐5 constituted a comparatively low, but highly variable proportion of humoral anti‐Dex antibodies of individual mice. In the present work we have analyzed by limiting dilution the expression of these two Id by anti‐Dex B cell precursors from the spleen and peritoneal cavity of BALB/c mice. Testing spleen cells we found about 65% of anti‐Dex precursors to be Id‐1+ and only a minority to be Id‐5+. Treatment with anti‐Ly‐1 and complement was without any effect on anti‐Dex precursors from spleen. Anti‐Dex B cell precursors among peritoneal cavity lymphocytes differed from those found in the spleen in two ways. First, on average, 50% of them were Id‐5+; second, about 80% carried the Ly‐1 marker. Both markers are, therefore, expressed on at least 30% of anti‐Dex B cell precursors from the peritoneal cavity but rarely on anti‐Dex precursors from the spleen.
Molecular analysis of VxIII variable regions of polyclonal rheumatoid factors during rheumatoid arthritis
Authors: Blaison Gilles , Kuntz Jean‐Louis , Pasquali Jean‐Louis 
Published: March 2007

AbstractWe report the first molecular characterization of Vx regions of the main human autoantibodies occurring during rheumatoid arthritis, the polyclonal rheumatoid factors. Using two sets of polymerase chain reactions in order to amplify the cDNA derived from both peripheral blood and synovial fluid rheumatoid factor‐secreting cells, nucleotide analysis of the VxIII family usage shows the following: (a) at least three different VxIII genes are used to encode polyclonal rheumatoid factors in a single patient, (b) each one of these genes seems more or less somatically mutated (from 1 to 14 mutations), (c) the mutation process preferentially affects the complementarity determining regions suggesting a selective pressure of antigen and (d) there is no clear difference between the mutation rates affecting the synovial fluid and peripheral blood rheumatoid factor‐secreting cells. These results are able to explain some of the known idiotypic differences between monoclonal and polyclonal rheumatoid factors in humans. They also provide evidence that polyclonal autoantibodies arising during an autoimmune disease can be the products of multiple somatically mutated genes and suggest that this process is antigen driven, whether this antigen is the Fc piece of IgG or another unknown antigen.
Transient depletion of T cells with high LFA‐1 expression from peripheral circulation during acute Plasmodium falciparum malaria
Authors: Hviid Lars , Theander Thor G. , Abdulhadi Nasreldin H. , Abu‐Zeid Yousif A. , Bayoumi Riad A. , Jensen James B. 
Published: March 2007

AbstractAcute P. falciparum malaria is associated with loss of in vitro T cell responsiveness to antigenic stimulation, and with high plasma levels of soluble interleukin 2 receptor (IL 2R). In the present study peripheral T cells from acute P. falciparum malaria patients from a malaria‐endemic area of Sudan were analyzed for expression of cell surface antigens associated with T lymphocyte adhesion, activation and maturation. The results were compared to results from T cells obtained from the same donors either before the attack, or during convalescence. Most donors showed a remarkable loss of T cells with high expression of the surface marker LFA‐1 (CD11a/CD18) during the clinical episode, in addition to the functional changes described above. Two donors that did not show phenotypic changes were furthermore characterized by having an unabated proliferative response and normal plasma IL2R levels. All peripheral CD3+ T lymphocytes expressed LFA‐1, which had a clearly bimodal distribution on these cells. The T cell subpopulation having high LFA‐1 expression (LFA‐1++) was composed of both memory and unprimed T cells, according to their expression of CD45RA and CD45R0. Analysis of expression of membrane‐bound IL 2R (CD25) and ICAM‐1 (CD54) did not reveal in vivo activated T cells in the peripheral blood of the patients. Taken together, these data suggest that circulating T cells recognizing parasite antigens are temporarily withdrawn from peripheral circulation during P. falciparum malaria.
Antigen presentation of hen egg‐white lysozyme but not of ribonuclease A is augmented by the major histocompatibility complex class II‐associated invariant chain
Authors: Nadimi Farsin , Moreno José , Momburg Frank , Heuser Andreas , Fuchs Serge , Adorini Luciano , Hämmerling Günter J. 
Published: March 2007

AbstractThe influence of the class II‐associated invariant chain (Ii) on the presentation of the protein antigens hen egg‐white lysozyme (HEL) and ribonuclease A (RNase) was investigated. For this purpose the Ii− rat‐2 fibroblasts were transfected with I‐Ak genes with or without Ii. Transfectants expressing Ii were superior in the presentation of the complete HEL protein to a panel of I‐Ak‐restricted T hybridomas characterized by distinct specificities for different HEL peptides and by different sensitivities to antigen concentration. There appeared to be a correlation between the antigen‐presenting capacity and the amount of Ii, in that transfectants expressing large amounts of Ii were the best antigen presentors. The presentation of synthetic HEL peptides was not infuenced by Ii.In contrast to the findings with HEL, the presentation of RNase by the same set of transfectants was clearly independent of Ii. Both antigens, HEL and RNase, required processing in the chloroquine‐sensitive compartment. However, only the presentation of HEL but not of RNase could be efficiently blocked by brefeldin A. These data confirm that presentation of HEL depends on de novo synthesized class II molecules, whereas the presentation of RNase seems to be predominantly mediated by a pool of pre‐existing class II molecules whose interaction with endocytosed antigen does not depend on Ii. These results suggest different mechanisms for the presentation of HEL and RNase and they raise the possibility that different antigens intersect the class II pathway at distinct intracellular locations.
Human eosinophils from hypereosinophilic patients spontaneously express the p55 but not the p75 interleukin 2 receptor subunit
Authors: Plumas Joël , Gruart Valérie , Aldebert Delphine , Truong Marie José , Capron Monique , Capron Audré , Prin Lionel 
Published: March 2007

AbstractThe expression of interleukin 2 receptor (IL 2R) on eosinophils was investigated in patients with hypereosinophilia. Hypodense activated eosinophils have been described in various diseases such as parasitic or allergic diseases, hypereosinophilic syndrome (HES) associated in some cases to myeloproliferative markers, and more recently described in patients undergoing recombinant IL 2 treatment. The presence of p55 α chain of IL 2R (CD25) on purified eosinophils collected from blood of hypereosinophilic patients was detected by flow cytometry. In 10 out of 19 cases, more than 10% of eosinophils were CD25+. Cross‐linking studies on enriched eosinophils showed one 64–75‐kDa band, consisting of IL 2 (15 kDa) cross‐linked to the IL2R p55 subunit. In Northern blot analysis the two messenger mRNA (3.5 and 1.5 kb) encoding the IL2R p55 subunit were identified after hybridization with a CD25 cDNA probe. In contrast, the presence of the IL2R p75 subunit was not detected. These data provide preliminary evidence for the expression of a low‐affinity receptor for IL 2 on in vivo activated eosinophils and raise the question of the role played by this cytokine in eosinophil differentiation and activation.
Calcium signals in single T cells on activation by lectin
Authors: Tregear Richard T. , Hoyland John , Mason William T. 
Published: March 2007

AbstractSuccinylation of concanavalin A (Con A) reduces its oligomer size while retaining its mitogenicity, and provides a probe of T cell activation. We have observed responses of cytosolic ionized calcium to succinyl Con A in suspensions of Jurkat and rat lymph node (LN) cells, using a fluorimeter, and in single cells settled on glass, using a dual wavelength video imaging system. In the fluorimeter a mitogenic level of succinyl Con A (30 μg/ml) produced only a 15–30 nM rise in average cell calcium in the suspended Jurkat or rat cells whereas the use of quantitative video imaging produced asynchronous 250–1000 nM pulses of free calcium in 35% of Jurkat cells and 300–850 nM pulses in 45% of rat LN cells. In Jurkat cells these pulses were sometimes repetitive, giving rise to apparent oscillations. In the fluorimeter 30 μg/ml of native Con A (a supra‐mitogenic concentration) produced a 300 nM rise in average cell calcium in suspended Jurkat cells, and a 100 nM rise in rat LN cells; when major histocompatibility complex class II‐bearing cells were removed the response rose. Mitogenic Con A (3 μg/ml) produced a much lower rise in calcium. With video imaging the response seen was greater. Levels > 30 μg/ml Con A caused 700–5000 nM pulses synchronously in 94% of Jurkat cells and 250–1000 nM pulses in 73% of rat LN cells. At 3 μg/ml Con A produced asynchronous 300–1100 nM pulses in 36% of rat LN cells. We conclude that the absence of a calcium signal in the fluorimeter can conceal asynchronous calcium responses in individual cells and that brief asynchronous cytosolic calcium pulses are sufficient for lectin to activate rat T cells.
T cell reactivity to an epitope of the mycobacterial 65‐kDa heat‐shock protein (hsp 65) corresponds with arthritis susceptibility in rats and is regulated by hsp 65‐specific cellular responses
Authors: Hogervorst Els J. M. , Boog Claire J. P. , Wagenaar Josée P. A. , Wauben Marca H. M. , van der Zee Ruurd , van Eden Willem 
Published: March 2007

AbstractAdjuvant arthritis (AA) can be induced in genetically susceptible rats by immunization with heat‐killed mycobacteria suspended in mineral oil. From our analysis of arthritogenic T cell clone A2b, obtained from an arthritic Lewis rat and specific for the 180–188 epitope of mycobacterial 65‐kDa heat‐shock protein (hsp 65), the possible origin of AA was explained by the existence of a molecular mimicry of the 180–188 epitope with a cartilage‐associated self antigen. We now have shown that Lewis rats respond to the 180–188 epitope after Mycobacterium tuberculosis immunization and that arthritis‐resistant Fisher and (Lewis × Fisher)F1 rats, although major histocompatibility complex class II identical with Lewis, do not respond to this epitope. However, in rare cases of arthritis in Fisher rats, responses to the epitope were seen. We obtained no evidence for a defect at the level of antigen processing and presentation or for suppression in Fisher rats. Thus, non‐responsiveness in Fisher rats was likely due to a difference at the level of the T cell repertoire.Previously, we have reported that pretreatment with hsp 65 in experimental arthritis, and not only in AA, caused resistance to arthritis induction. We now present evidence that immunization with hsp 65 or in vitro stimulation with hsp 65 may lead to inhibition of responses specific for epitope 180–188. Thus the hsp 65‐induced resistance to arthritis is probably caused by the induction of regulatory control specifically targeted at the 180–188 epitope. Especially in rats that tend to focus their responses on the critical 180–188 sequence, such as Lewis, regulation seems to develop following immunization with hsp 65. Since recent evidence suggests that hsp 65 and also the 180–188 epitope have a role in human arthritic conditions, the present findings are expected to contribute to further experimentation directed at exploiting hsp 65 or its epitopes for the development of new therapeutical approaches in humans.
VH gene usage in humans: biased usage of the VH6 gene in immature B lymphoid cells
Authors: Berman Jeffrey E. , Nickerson Katherine G. , Pollock Roberta R. , Barth Jeremy E. , Schuurman Ruud K. B. , Knowles Daniel M. , Chess Leonard , Alt Frederick W. 
Published: March 2007

AbstractPreferential usage of JH‐proximal VH genes has been demonstrated in immature murine B cell repertoires. To determine whether this phenomenon is also evident in human repertoires, we studied utilization of VH6, the most JH‐proximal human VH gene. Examination of VH gene usage in a panel of precursor B cell acute lymphoblastic leukemia samples indicated that 15% of the IgH rearrangements utilized VH6. VH6 is a single‐member family in a total repertoire of 100–200 VH genes; thus, if usage were purely random, one would expect VH6 rearrangement frequency to be < 1%. Analysis of VH gene usage in normal lymphoid tissues also revealed biased usage of VH6. VH6 was preferentially utilized in 16‐ to 24‐week‐old fetal liver as compared to adult peripheral blood mononuclear cells or spleen. Possible implications of the conservation of preferential usage of JH‐proximal genes in both immature murine and human repertoires are discussed.
Amino acid sequence analysis of a mouse interleukin 5 receptor protein reveals homology with a mouse interleukin 3 receptor protein
Authors: Devos René , Vandekerckhove Joel , Rolink Antonius , Plaetinck Geert , van der Heyden José , Fiers Walter , Tavernier Jan 
Published: March 2007

AbstractA polypeptide chain for the mouse interleukin 5 receptor (IL5R) was purified from detergent‐lysed B13 cells, a mouse IL5‐dependent pre‐B cell line. Purification was by a single immunoaffinity chromatographic step using an anti‐mouse IL 5R monoclonal antibody, R52. Internal amino acid sequence was obtained from four trypsin‐generated peptides. All peptides were found to be present in the published amino acid sequence of a mouse IL 3R and the mouse IL 3R‐like protein deduced from the cDNA. This indicates that the mouse IL 5R and the mouse IL 3R have a homologous polypeptide in common and suggests that the specificity of these lymphokine receptors is mainly generated by association with another ligand‐specific polypeptide chain.
Anti‐T cell receptor antibody treatment of rats with established autologous collagen‐induced arthritis: suppression of arthritis without reduction of anti‐type II collagen autoantibody levels
Authors: Goldschmidt Tom J. , Holmdahl Rikard 
Published: March 2007

AbstractActivation of T cells is critical for the development of type II collagen (CII)‐induced arthritis (CIA). However, the relative importance of T cells in their delivery of help to B cells, promoting autoantibody formation or acting as inflammatory initiating cells, is unclear. The effect of a monoclonal antibody directed to the α/β T cell receptor (TcR) on the development of autologous CIA was studied. Two weeks after immunization with autologous CII the onset of severe arthritis occurred, followed by a chronic arthritis activity in the peripheral joints. Anti‐TcR treatment before immunization suppressed the incidence of arthritis and the autoantibody response to CII. Treatment given immediately before the expected onset delayed the appearance of arthritis. Treatment given to already arthritic rats reduced the severity. In the latter two groups the serum levels of anti‐CII autoantibodies were not affected. The duration of the ameliorating effect was limited and with the return of arthritis a concomitant antibody response towards the injected mouse anti‐TcR antibody was observed. These results show that the role of T cells in both the induction and perpetuation of CIA is essential and not limited to the triggering of production of pathogenic anti‐CII autoantibodies.
Cross‐protection against influenza A virus infection by passively transferred respiratory tract IgA antibodies to different hemagglutinin molecules
Authors: Tamura Shin‐Ichi , Funato Hirono , Hirabayashi Yoshihiro , Suzuki Vujiro , Nagamine Takashi , Aizawa Chikara , Kurata Takeshi 
Published: March 2007

AbstractMice that were intranasally immunized with different influenza A virus hemagglutinins (HA), derived from PR8 (H1N1), A/Yamagata (H1N1) or A/Fukuoka (H3N2) virus, together with cholera toxin B subunit as an adjuvant, were examined for protection against PR8 infection; PR8 HA and A/Yamagata HA immunization conferred complete protection, while A/Fukuoka HA immunization failed to confer protection. In parallel with protection, PR8 HA‐, A/Yamagata HA‐, and A/Fukuoka HA‐immunized mice produced a high, a moderate and a low level of PR8 HA‐reactive IgA in the respiratory tract, respectively. These IgA antibodies were not only higher in content in the nasal secretions, but also more cross‐reactive than IgG. The purified IgA antibodies from respiratory tract washings of PR8 HA‐immunized mice, which contained the HA‐specific IgA corresponding to the amount deteced in the nasal wash, were able to protect mice from PR8 challenge when transferred to the respiratory tract of naive mice. The transfer of IgA from A/Yamagata HA‐immunized mice also afforded cross‐protection against PR8 infection, whereas the IgA from A/Fukuoka HA‐immunized mice failed to provide protection. The ability of transferred IgA to prevent viral infection was dependent on the amount of HA‐reactive IgA remaining in the respiratory tract of the host at the time of infection. These experiments directly demonstrate that IgA antibodies to influenza A virus HA by themselves play a pivotal role in defence not only against homologous virus infection, but also against heterologous drift virus infection at the respiratory mucosa, the portal of entry for the viruses.