bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetics of peritoneal B‐1a cells (CD5 B cells) in young adult mice
Authors: Deenen Gerrit Jan , Kroese Frans G. M. 
Published: March 2007

AbstractIn the mouse, conventional B cells are continuously generated from precursor cells located in the bone marrow (BM), whereas the small subset of B‐1 cells (formerly called Ly‐1 B cells) constitute a self‐replenishing population of cells. Here we studied the kinetics of murine peritoneal B‐1a cells (i.e. B‐1 cells expressing CD5). The actual number of B‐1a cells in the peritoneal cavity that are proliferating, as detected by metaphase arrest and S‐phase index, was below detection level, indicating that these cells do not divide significantly at this anatomical location. To establish the life‐span of B‐1a cells we used long‐term administration of 5‐bromo‐2′‐deoxyuridine in combination with three‐color immunocytology on cytospin preparations. The renewal rate of peritoneal B‐1a cells was 1.3% per day representing a 50% renewal time of 38 days. Splenic B cells and popliteal lymph node B cells (predominantly conventional B cells) showed an almost identical renewal rate of 1.1% per day. The data show that peripheral B cells from various lymphoid tissues and locations do not differ significantly in their renewal capacity, even though there are differences in their developmental origin.
T suppressor hybridomas and interleukin‐2‐dependent lines induced by copolymer 1 or by spinal cord homogenate down‐regulate experimental allergic encephalomyelitis
Authors: Aharoni Rina , Teitelbaum Dvora , Arnon Ruth 
Published: March 2007

AbstractSuppressor T (Ts) hybridomas and interleukin‐2‐dependent T cell lines were established from spleens of mice, which had been rendered unresponsive to experimental allergic encephalomyelitis (EAE) either by mouse spinal cord homogenate or by the synthetic suppressant copolymer 1 (Cop 1). The Ts hybridoma supernatants and the Ts line cells specifically suppressed the in vitro response to the encephalitogenic myelin basic protein (BP), as indicated by inhibition of both the proliferation and interleukin‐2‐secretion responses of a BP‐specific T cell line. Moreover, these Ts cells prevented the development of actively induced EAE in vivo. All hybridomas and lines were most effective when injected at the time of disease induction, thus suggesting that they operate as effector suppressor cells, and functionally inhibit encephalitogenic responses. The data presented here suggest that the suppressor cells are stimulated by the protective epitopes included in the BP as well as in the Cop 1 molecules and that they play an active role in the regulation of EAE. The generation of Ts lines and hybridomas, which have been induced by Cop 1, establish the specific stimulation of suppressor cells to EAE as a mechanism underlying the therapeutic activity of Cop l.
Split tolerance of Thl and Th2 cells in tolerance to Theiler's murine encephalomyelitis virus
Authors: Peterson Jeffrey D. , Karpus William J. , Clatch Richard J. , Miller Stephen D. 
Published: March 2007

AbstractTheiler's murine encephalomyelitis virus (TMEV) produces a chronic, inflammatory demyelinating disease in susceptible mouse strains that is used as a model for multiple sclerosis. Because disease susceptibility correlates temporally with the development of virus‐specific delayed‐type hypersensitivity (DTH) responses, we studied methods and mechanisms by which virus‐specific DTH could be specifically inhibited. The intravenous injection of UV‐inactivated TMEV coupled to syngeneic splenocytes via a carbodiimide linkage (TMEV‐SP), prior to immunization, induced a significant degree of tolerance in virus‐specific helper (Th) cells as determined by decreased DTH and T cell proliferative responses, and decreased interleukin (IL)‐2 and interferon (IFN)‐Y protein and mRNA levels. In contrast to the reduced levels of Thl‐specific lymphokine mRNA levels, IL‐4‐specific mRNA levels in response to virus stimulation were not affected in tolerant mice. Surprisingly, the total anti‐TMEV antibody response in DTH tolerant mice was enhanced 20‐100‐fold over sham‐tolerized controls and was composed of reduced levels of anti‐virus IgG2a, but dramatically increased levels of anti‐virus IgGl. The “split‐tolerance” was antigen specific, dependent on the concentrations of TMEV and carbodiimide used in the coupling procedure, and varied with the number of coupled syngeneic splenocy tes administered. The fixative effects of carbodiimide on antigen‐presenting function were necessary for the induction of DTH tolerance with TMEV‐SP, since intravenous administration of virus coupled to splenocytes via a biotin‐avidin linkage led to enhanced virus‐specific antibody responses, but was unable to inhibit DTH unless concomitantly fixed with carbodiimide. Collectively, the data indicate that Thl cells (mediating DTH, IL‐2 and IFN‐γ production, and helper function for IgG2a production) were specifically anergized, with concomitant stimulation of Th2 cells (producing IL‐4 and mediating helper function for IgGl antibody production).
Mechanisms that generate human immunoglobulin diversity operate from the 8th week of gestation in fetal liver
Authors: Cuisinier Anne‐Marie , Gauthier Laurent , Boubli Léon , Fougereau Michel , Tonnelle Cécile 
Published: March 2007

AbstractThe repertoire of immunoglobulin expressed very early in human development was approached by cloning and sequencing 55 rearranged and 11 germ‐line VH transcripts, after amplification by polymerase chain reaction of cDNA libraries derived from two fetal livers at 8 and 13 weeks of gestation. All families with the exception of VH2, were expressed as soon as 8 weeks, with preferential usage of certain germ‐line genes. Very few somatic mutations, randomly localized, were identified. By contrast, in a series of clones derived from the same VDJ rearrangement using the VH6 family, extensive mutations had taken place, mostly accumulated in the third complementarity‐determining region (CDR3) suggesting that the specialized enzymatic machinery was at hand very early during human development.Some other characteristics of the fetal repertoire also emerged, namely increased usage of JH3 and JH2, as compared to the adult pattern, where JH4 is dominant and reduced length of the D/CDR3 regions. All D gene families were identified, and their usage frequently involved D‐D fusions. N diversity was present very early, and increased with age.Identification of germ‐line transcripts pertaining to all six VH families including pseudogenes, in the E55 library, revealed a population very different as compared to rearranged gene transcripts. This suggests that a large portion of VH locus is accessible for transcription, bringing no evidence of correlation between preferential rearrangement of a given VH gene and its localization in the locus.
Alterations of CD2 association with T cell receptor signaling molecules in “CD2 unresponsive” human T lymphocytes
Authors: Schraven Burkhart , Wild Martin , Kirchgessner Henning , Siebert Brigitte , Wallich Rainer , Henning Stefan , Samstag Yvonne , Meuer Stefan C. 
Published: March 2007

AbstractCD2‐associated molecules were identified by means of in vitro kinase assays of CD2 immunoprecipitates obtained from nontransformed human T lymphocytes lysed in the detergent brij 58. Under these conditions CD2 was found to be associated with the protein tyrosine kinases p56lck and p59fyn as well as two low molecular weight phosphoproteins. The latter were identified as the ζ and ϵ chains, the major signaling components of the CD/7 TcR complex. Importantly, induction of T cell unresponsiveness towards CD2‐mediated stimuli by means of CD3/Tcell receptor (TcR) modulation results in uncoupling of ζ and ϵ from the CD2 molecule, while its associations with p56lck and p59fyn remain unaffected. Moreover, despite the incapacity of T lymphocytes to undergo DNA synthesis in the CD3/TcR‐modulated state, CD2 triggering still results in tyrosine phosphorylation of some unknown protein substrates. Thus, the same ζ and ϵ chains which are components of a functional TcR complex appear to also couple to the CD2 molecular complex. Moreover, dissociation of TcR and CD2 complexes in intact cells seems to block CD2‐mediated Tcell growth but does not result in complete abolishment of the signal transducing capacity of the CD2 receptor.
Fine specificity and VJ usage of light chains in antibodies to the phosphorylcholine hapten
Authors: Lötscher Marcel , Heusser Christoph H. , Amstutz Hanspeter , Blaser Kurt 
Published: March 2007

AbstractIn the memory response to the phosphorylcholine hapten (PC) two major groups of anti‐PC antibodies with different fine specificities are elicited. Group I antibodies are mainly PC specific, whereas Group II antibodies are comprised of two specificities directed against the phenyl‐PC and the phenyl moiety of the PC hapten. The VL gene usage of 17 monoclonal memory anti‐PC antibodies were investigated by Southern blot analysis and nucleotide sequencing. Six out of eight Group I memory PC‐specific antibodies used the same VK22‐JK5 rearrangement as the major T15 primary response idiotype. One expressed a mutated JKI and one employed another VK22 gene family member. A shift in specificity from PC (Group I) towards phenyl‐PC (Group II) was accompanied with the usage of either VK1C‐JK1 or VK1A‐JK5 rearrangements. The phenyl‐specific Group II antibodies expressed the Vλl‐Jλ L chain rearrangement in combination with VH M141 expressing H chains. In this specific segment of Group II antibodies most mutations were found. Thus four different VL genes were found to contribute to the fine specificity of memory response antibodies to the PC hapten in a clear structure‐function relationship. The diversified fine specificity in the memory response derives mainly from the usage of different L chains with particular VJ rearrangements in combination with VH of the dominant initial response clonotype and is not primarily due to mutational events.
Correlation between cell‐mediated immunity and degree of infection in subjects living in an endemic area of schistosomiasis
Authors: de Jesus Amelia M. Ribeiro , Almeida Roque P. , Bacellar Olivia , Araujo Maria Ilma , Demeure Christian , Bina Jose Carlos , Dessein Alain J. , Carvalho Edgar M. 
Published: March 2007

AbstractCell‐mediated immunity to Schistosoma mansoni antigens, unrelated antigens and mitogens was evaluated in 50 subjects with the same degree of exposure to infection living in an endemic area of schistosomiasis. The degree of infection, assessed by the number of eggs/g of stool, was variable in this population (0‐5604), suggesting differences in susceptibility to infection. Absence of lymphoproliferative response was observed in 56% of this group, despite having a response to purified protein derivative of tuberculin (PPD) and tetanus toxoid (TT) antigens and to pokeweed mitogen. The 50 subjects were divided into two groups, according to their degree of infection. The lymphoproliferative responses to schistosomula and adult worm antigens in the group with a low degree of infection (≤400 eggs/g of stool) were higher than the ones documented in patients with a high degree of infection (>400 eggs/g of stool), and these differences were statistically significant (p ≤0.001). An inverse correlation between the lymphocyte proliferation in response to S. mansoni antigens and the degree of infection was also observed (p = 0.02), indicating that subjects with a lower degree of infection have a higher lymphoproliferative response to schistosomula and adult worm antigens. No differences in the lymphocyte reactivity to other antigens (PPD and TT) were detected in these groups. An impairment of interferon‐γ in vitro production was observed when the lymphocytes from these subjects were stimulated with S. mansoni adult worm antigen, although they produced gamma interferon in response to phytohemag‐glutinin.
Characterization of four novel ϵ chain mRNA and a comparative analysis of genes for immunoglobulin E in rodents and man
Authors: Hellman Lars 
Published: March 2007

AbstractThe nucleotide sequence of the 3′ region of the E chain gene for human IgE is presented. A comparison of the entire region from 5′ of exon C1 to the M2 exon of the mouse, rat and human ϵ chain genes shows that the overall structure of the ϵ chain gene have changed only minimally during the 60‐70 million years of evolutionary separation between rodents and man.We have previously shown that a number of rearrangements larger than 10 bp have relatively recently occurred in the C4/M1 intron of the rat or the mouse E chain genes. A majority of these rearrangements were found within or in close proximity to repetitive sequences of Z‐DNA‐forming potential (CA dinucleotide repeats). The C4/M1 intron has evolved very rapidly, to such an extent that no apparent homology can be detected between rodents and man. Only remnants of the repetitive sequences are present in man, supporting the theory that repetitive sequences having Z‐DNA‐forming properties may play a role in the evolution of the eucaryote genome by promoting recombinations, leading to a rapid evolutionary drift of sequences in close proximity to these repeats.We report here the characterization of the membrane domains of human IgE and four novel mRNA transcribed from the human E chain locus. The primary structures have been determined by polymerase chain reaction cloning and nucleotide sequence analysis. All five mRNA contain the C3 domain and the membrane exon 2 (M2). Due to frame shifts caused by novel splice sites or novel splice‐site combinations, the proteins encoded by three out of these four novel mRNA differ in their carboxy‐terminal end from the classical secreted or membrane‐bound immunoglobulins. Northern blot analysis shows significant levels of at least three out of these four novel mRNA in an IgE‐producing human cell line.One of the mRNA encodes a transmembrane‐like structure which has characters in common with the transmembrane region of the CD3 components of the T cell receptor complex (CD3 γ,δ and ϵ). This indicates that IgE‐producing B cells possibly have two separate signal‐transducing systems.A comparison of the classical membrane anchoring domain of the human ϵ chain with a panel of immunoglobulin membrane domains from fish to higher mammals is presented. A tyrosine and a glutamine residue is found to be conserved between all cytoplasmic domains of all post‐switch immunoglobulin classes indicating a functional conservation of these amino acid residues. Suggested functions for these residues are their participation in signal transduction or in linkage to the cytoskeleton for internalization of antibody‐antigen complexes.
Inhibition of human immunodeficiency virus infection by the lectin jacalin and by a derived peptide showing a sequence similarity with gp120
Authors: Favero Jean , Corbeau Pierre , Nicolas Michel , Benkirane Monsef , Travé Gilles , Dixon James F. P. , Aucouturier Pierre , Rasheed Surayia , Parker John W. , Liautard Jean Pierre , Devaux Christian , Dornand Jacques 
Published: March 2007

AbstractJacalin is a plant lectin known to specifically induce the proliferation of CD4+ T lymphocytes in human. We demonstrate here that jacalin completely blocks human immunodeficiency virus type 1 (HIV‐1) in vitro infection of lymphoid cells. Jacalin does not bind the viral envelope glycoprotein gp120. Besides other T cell surface molecules, it interacts with CD4, the high‐affinity receptor to HIV. Binding of jacalin to CD4 does not prevent gp120‐CD4 interaction and does not inhibit virus binding and syncytia formation. The anti‐HIV effect of the native lectin can be reproduced by its separated a‐subunits. More importantly, we have defined in the a‐chain of jacalin a 14‐amino acid sequence which shows high similarities with a peptide of the second conserved domain of gpl20. A synthetic peptide corresponding to this similar stretch also exerts a potent anti‐HIV effect. This peptide is not mitogenic for peripheral blood mononuclear cells and does not inhibit anti‐CD3‐induced lymphocyte proliferation. These results make jacalin a chain‐derived peptide a potentially valuable therapeutic agent for acquired immunodeficiency syndrome.
Development of T cell receptor αβ‐bearing T cells in the submersion organ culture of murine fetal thymus at high oxygen concentration
Authors: Watanabe Yoshihiro , Katsura Yoshimoto 
Published: March 2007

AbstractOrgan culture (OC) of murine fetal thymuses on a membrane filter floating on the medium has been used as an important strategy in studies of the mechanism of T cell development. On the other hand, the submersion organ culture (S‐OC) system, in which fetal thymus lobes are submerged in the culture medium, is not popularly used because the growth of T cells is much lower than that in OC at the air‐medium border (AMB‐OC). In the present work, we tried to culture the fetal thymuses in the S‐OC system at 5% CO2 and various concentrations of O2. We found that in the environment containing 5% O2, γδ cells were selectively generated, though the cell recovery was less than one‐tenth of that seen in AMB‐OC. Generation of γδ T cells was hardly affected by increasing the O2 concentration. In marked contrast, the development of αβ T cells was highly dependent upon the O2 concentration. In the S‐OC at more than 60% O2, differentiation and growth of T cells, as determined in terms of recovered cell number, CD4 vs. CD8 profile and predominance of αβ lineage, were comparable to those observed in AMB‐OC. It was further shown that clonal deletion of Vβ6+ T cells occurred in high O2 S‐OC of CBA/J (Mls‐1a) but not C3H/HeJ (Mls‐1b) mice, the extent of the deletion being low but comparable with that seen in AMB‐OC. These results indicated that the fetal thymus microenvironment was potentially capable of supporting the development of both γδ and αβ T cells, and that skewing to one of these lineages was determined by an additional factor(s) such as the concentration of O2 dissolved in the medium.
Optimization of primers for cloning libraries of mouse immunoglobulin genes using the polymerase chain reaction
Authors: Kettleborough Catherine A. , Saldanha José , Ansell Keith H. , Bendig Mary M. 
Published: March 2007

AbstractWe have optimized primers for cloning libraries of murine heavy and light chain variable regions using the polymerase chain reaction. Since we are interested in cloning murine Fab fragments for expression in bacterial cells, the heavy chain primers were designed to clone Fd fragments comprising the heavy chain variable domain and the first domain of the IgG constant region. The light chain primers were designed to clone the entire murine kappa chain. Using ten degenerate 5′ primers and a degenerate 3′ primer to amplify murine Fd and seven degenerate 5′ primers with a single 3′ primer to amplify kappa chains, a diverse repertoire of mouse variable regions was cloned from mouse spleens.
Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF‐a and TNF‐0 by human mononuclear cells: a possible link to insulin‐dependent diabetes mellitus
Authors: Pociot Flemming , Briant Laurence , Jongeneel C. Victor , Mölvig Jens , Worsaae Helle , Abbal Michel , Thomsen Mogens , Nerup Jørn , Cambon‐Thomsen Anne 
Published: March 2007

AbstractWe have investigated the correlation between different tumor necrosis factor (TNF) and class II major histocompatibility complex alleles in the lipopolysaccharide‐ or phytohemagglutinin‐induced secretion of TNF‐α and TNF‐β by human monocytes and peripheral blood mononuclear cells in 87 unrelated Danish male individuals. Significant differences in TNF‐α secretory capacity between TNF Ncol restriction fragment length polymorphisms, TNFa and TNFc micro‐satellite alleles and DR alleles were identified. No correlation with TNF‐β secretory capacity was found for any of the markers studied. TNF genotyping allowed us to define four extended HLA haplotypes which correlate with TNF‐α secretory capacity. Two of these are DR4 positive: DQw8, DR4, TNFB*1, TNFa6, B44, A2 and DQw8, DR4, TNFB*2, TNFa2, B15, A2. Individuals carrying the TNFB*2, TNFa2 haplotype had a higher TNF‐α secretory capacity than those carrying the TNFB*1, TNFa6 haplotype. In a group of DR3/DR4 heterozygous patients with insulin‐dependent diabetes mellitus (IDDM), the frequency of the TNFa2 allele was higher than in HLA‐DR matched controls, whereas theTNFa6 allele was more frequent in control individuals. In the DR3/DR4 heterozygous diabetic group 12/26 had the alleles combination DQw8, DR4 (Dw4), C4A3, TNFB*2, TNFa2, B15, whereas only 1/18 controls had this haplotype. This diabetogenic haplotype is identical to the DR4 haplotype which correlates with a higher TNF‐α response. These observations suggest a direct role for the TNF locus in the pathogenesis of IDDM.
Functional double‐negative T cells in the periphery express T cell receptor Vβ gene products that cause deletion of single‐positive T cells
Authors: Martínez‐a Carlos , Marcos Miguel A. R. , de Alboran Ignacio M. , Alonso José María , de Cid Rafael , Kroemer Guido , Coutinho Antonio 
Published: March 2007

AbstractA proportion of peripheral T cells lack surface expression of the CD4 or CD8 coreceptor molecules and hence are designated as “double negative” (DN). Most DN T lymphocytes express the Γ/β T cell receptor (TcR), but a minor fraction of them, in both humans and mice, express the α/β TcR. Whereas α/β+ DN T lymphocytes are infrequent (< 1%) in conventional lymphoid organs (spleen, blood, lymph node), they account for two‐thirds of the T cells residing in adult bone marrow. Analysis of the TcR Vβ repertoire expressed by peripheral DN T cells revealed a high frequency of cells bearing autoreactive TcR that cause deletion of “single‐positive” (SP) (CD4+CD8− or CD4−CD8+) T cells. Peripheral DN cells thus represent a cell type that is relatively resistant to clonal deletion. Furthermore, such cells have not been inactivated (anergized) in vivo since they proliferate and secrete interleukins in response to cross‐linking by monoclonal antibodies specific for these Vβ gene products that are deleted in SP T cells. These results might help to understand the association of peripheral expansion of DN cells and development of autoimmune diseases.
Role of flanking variable sequences in antigenicity of consensus regions of HIV gp120 for recognition by specific human T helper clones
Authors: Manca Fabrizio , Habeshaw John A. , Dalgleish Angus G. , Fenoglio Daniela , Pira Giuseppina Li , Sercarz Eli E. 
Published: March 2007

AbstractHuman T helper cells can discriminate among strain variants of HIV gp120 because of T cell clones recognizing non‐conserved regions, as demonstrated with T cells from HIV‐infected individuals and vaccinated volunteers and with primary T cell lines and clones obtained by in vitro immunization.To obtain a better definition of cross‐reactions among T cell determinants within HIVgp120 variants, we used a panel of analog peptides within residues 236‐251 from the BRU, MN, SF2 and RF strain sequences to induce primary human T cell lines and clones. Different patterns of response were obtaind using each of the analog peptides, although they all share the consensus sequence 246‐251. Clones recognizing this sequence were generated by priming with the BRU and RF analog peptides, but not with the SF2 analog peptide. SF2 did not induce any 242‐245‐specific clones, but only T cells recognizing the 236‐240 sequence. A preferential response to residues 236‐240 was obtained by priming with the BRU and SF2 peptides, but not with the MN and RF peptides.These results suggest that although the analog peptides exhibit a high degee of homology and share a consensus of the C‐terminal sequence (246‐251), the T cell response to the conserved sequence 246‐251 is controlled by flanking sequences. Therefore the presence of a shared sequence per se does not imply in vitro expansion of clones with that fine specificity, even though such clones are available within the naive repertoire and can be triggered by an analog peptide.