bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell surface expression of the short immunoglobulin μ chain (Dμ protein) in murine pre‐B cells is differently regulated from that of the intact μ chain
Authors: Tsubata Takeshi , Tsubata Rieko , Reth Michael 
Published: March 2007

AbstractPre‐B cells carrying DJH rearrangements in an appropriate reading frame produce a short μ protein consisting of a DJH and the Cü & sequence (ü protein). We analyzed a Dμ‐producing Abelson‐murine leukemia virus‐transformed murine pre‐B line, 300–19, and demonstrated that Dμ proteins are expressed on the cell surface in association with surrogate L chain proteins (Λ5 and VpreB). However, when we introduced an expression vector coding for the Dμ protein into the null pre‐B line P17–27, which produce Λ5 and VpreB but no Ig molecules, most of the cells did not express Dμ proteins on the cell surface although Dμ proteins were produced intracellularly. On the other hand, P17–27 brings intact μ chains on the cell surface, when a vector coding for the intact μ chain is introduced. Thus, cell surface expression of the Dμ protein has different requirements from that of the intact μ chain. A possible role of the VH protein encoded by germ‐line VH transcripts is discussed.
Interleukin 1‐induced maturation of progenitor thymocytes
Authors: Takashi Tohru , Gause William C. , Wilkinson Miles , Macleod Carol L. , Steinberg Alfred D. 
Published: March 2007

AbstractRegulation of thymocyte development was assesed by culturing purified CD4−CD8− thymocytes with cytokines. Sorted CD3−CD4−CD8− adult thymocytes responded to the combination of interleukin (IL) 1 plus IL 2 without additional mitogens or co‐mitogens with both cellular proliferation and cell surface expression of the T cell receptor (TcR)/CD3 complex. IL 2 alone induced neither proliferation nor cell surface TcR/CD3 expression. IL 1 alone was sufficient to induce cell surface TcR/CD3 without proliferation. Prior to stimulation with cytokines, the progenitor CD4−CD8− thymocytes accumulated TcR β and CD3 γ, δ, ε and ϱ, mRNA but TcR α mRNA was not detectable. Stimulation with IL 1 led to a dramatic induction of TcR α mRNA without an increase in the other transcripts. These studies suggest that IL 1 regulates the differentiation status of immature adult thymocytes. Nuclear run‐on studies suggested that the increase in TcR α mRNA accumulation induced by cytokines might result from post‐transcriptional accumulation.
Stimulation of B lymphocytes via CD72 (human Lyb‐2)
Authors: Kamal Mohammed , Katira Anita , Gordon John 
Published: March 2007

AbstractA monoclonal antibody to CD72, the 45‐kDa human homolog of marine Lyb‐2, was found to augment selective activation pathways in tonsillar B lymphocytes. By itself, CD72 antibody provided a weak direct stimulus to resting B cells as assessed by [3H]dThd incorporation; this was modestly enhanced on the addition of interleukin 4 (IL 4) or following ligation of surface CD40. CD72‐delivered signals were more evident in co‐stimulation assays with phorbol ester and with a synergistic combination of IL 4 and CD40 antibody, but not with calcium ionophore or a CD23 antibody; rapidly cycling B cells were refractory to signaling via CD72 whether or not other co‐stimuli were present. A unique feature of the CD72‐delivered signal was its ability to enhance synergistically stimulations triggered with immobilized antibody to IgM, while failing to augment responses initiated by soluble anti‐μ. On direct culture of resting B lymphocytes with CD72 antibody, an approximately twofold increase in the expression of major histocompatibility complex class II DQ antigen was observed, an augmentation similar to that achieved with IL 4; CD72 antibody also mimicked IL 4 in its ability to drive G0 cells into the early G1 phase of cell cycle. In contrast to IL 4‐promoted stimulation, CD72 antibody failed to up‐regulate the surface expression of either IgM or the CD23 antigen. CD72 expression itself was found to be weak on resting B lymphocytes and was modestly enhanced following culture with IL 4. The findings are discussed with reference to observations made on the triggering of murine B lymphocytes through Lyb‐2 and within the context of previously defined human B cell activation pathways.
Identity of human Lyb‐2 and CD72 and localization of the gene to chromosome 9
Authors: von Hoegen Ilka , Hsieh Chih‐Lin , Scharting Roland , Francke Uta , Parnes Jane R. 
Published: March 2007

AbstractWe have recently reported the isolation of cDNA clones encoding the human homolog of the mouse B cell differentiation antigen Lyb‐2. Expression of Lyb‐2 is restricted to B lineage cells and turned off in antibody‐secreting plasma cells in both mice and humans. Functional studies with anti‐mouse Lyb‐2 monoclonal antibodies (mAb) suggest that this protein may be involved in signals for B cell proliferation. We now describe the generation of mAb specific for human Lyb‐2. Furthermore, we demonstrate that the human Lyb‐2 protein is recognized by a mAb specific for the newly clustered pan B cell surface antigen CD72, which had been defined by mAb. Mouse L(tk−) cells expressing a transfected cDNA encoding human Lyb‐2 bind a mAb specific for CD72. We further show that an antiserum and a mAb specific for human Lyb‐2 and an anti‐CD72 mAb immunoprecipitate the identical protein from human splenic B cells and B cell lines, as well as from transfected L(tk−) cells. These data indicate that CD72 is the human equivalent of mouse Lyb‐2. We have additionally localized the gene for human Lyb‐2/CD72 on the short arm of chromosome 9. Mouse Lyb‐2 had been previously mapped to mouse chromosome 4. Lyb‐2/CD72 is now the tenth gene known to be localized on human chromosome 9 and mouse chromosome 4.
Autoreactive T and B cells responding to myelin proteolipid protein in multiple sclerosis and controls
Authors: Sun Jia‐Bin , Olsson Tomas , Wang Wei‐Zhi , Xiao Bao‐Guo , Kostulas Vasilios , Fredrikson Sten , Ekre Hans‐Peter , Link Hans 
Published: March 2007

AbstractThe pathogenesis of multiple sclerosis (MS) could involve an autoimmune response to proteolipid protein (PLP). Immunization of experimental animals with this major myelin protein can lead to experimental allergic encephalomyelitis. To identify a possible role of PLP as target antigen in MS, we evaluated T celi immunity to PLP in blood and cerebrospinal fluid (CSF) from patients with MS and controls by counting cells which in response to PLP in short‐term cultures secreted interferon‐γ. The PLP‐specific B cell response was analyzed by counting cells secreting anti‐PLP antibodies. PLP‐reactive T cells were detected in blood of most MS patients (mean value 1 per 20408 mononuclear cells), and at 41‐fold higher numbers in CSF (mean 1 per 500 CSF cells). Anti‐PLP IgG antibody‐secreting cells were detected in blood from most MS patients (mean 1 per 30303 cells), but such cells were 49‐fold more frequent in CSF (mean 1 per 625 cells). PLP‐reactive T and B cells were also detected in blood and CSF from control patients, but at much lower numbers. A strong and persistent autoimmune response to PLP as well as to other myelin proteins, enriched in CSF, is proposed to be pathogenetically important in MS.
Molecular characterization of an IgA receptor from group B streptococci: sequence of the gene, identification of a proline‐rich region with unique structure and isolation of N‐terminal fragments with IgA‐binding capacity
Authors: Hedén Lars‐Olof , Frithz Elisabet , Lindahl Gunnar 
Published: March 2007

AbstractCertain strains of group B streptococci express a cell surface protein that binds IgA and acts as a virulence factor. This IgA receptor is referred to here as protein Bac. The gene for protein Bac was cloned and expressed in Escherichia coli, and the complete nucleotide sequence was determined. The deduced amino acid sequence of 1134 residues includes a signal sequence of 37 amino acids and a putative membrane anchor region at the C‐terminal end. The processed form of the receptor, 1097 residues, has a calculated molecular weight of 123 786. There are no cysteines in protein Bac, suggesting a fibrillar structure. The C‐terminal half of the protein includes a 90 residues long region with a novel type of periodic structure, the “XPZ motif”, in which every third amino acid is proline. Unlike other bacterial immunoglobulin‐binding proteins, there are no long repeats in protein Bac. Clones which express only part of the protein Bac gene were used to show that IgA‐binding takes place in the N‐terminal part of the molecule. Protein Bac was originally described as an antigen called β, but N‐terminal fragments that bind IgA do not react with a reference serum against the β antigen. These and other data indicate that protein Bac can be divided into two regions with different functions: an N‐terminal IgA‐binding region and a C‐terminal region corresponding to the β antigen. The IgA‐binding region of protein Bac does not show any homology to protein Arp, the IgA receptor from group A streptococci, although these receptors have similar binding properties. This indicates that convergent evolution has favored the appearance of these two structurally different streptococcal IgA receptors.
Molecular heterogeneity of the 1.0‐kb Tβ transcript in natural killer and γ/δ lymphocytes
Authors: Fagioli Marta , Care Alessandra , Ciccone Ermanno , Moretta Lorenzo , Moretta Alessandro , Meccia Ettore , Testa Ugo , Fallnl Brunangelo , Grignani Fausto , Peschle Cesare , Pelicci Pier Giuseppe 
Published: March 2007

AbstractThe T cell receptor (TcR) β chain is encoded by a 1.3‐kb mRNA which contains variable (V), diversity (D), joining (J) and constant (C) regions, A shorter 1.0‐kb transcript with C but no V sequences is found in thymocytes, α/β and γ/δ T lymphocytes and natural killer cells. The origin, clonal variability and function of this transcript is unknown. We isolated cDNA clones representative of the 1.0‐kb mRNA from cDNA libraries of either polyclonal or clonal natural killer and γ/δ lymphocytes. Ten different types of cDNA clones belonging to three separate groups were identified: (a) “J‐C clones” consisting of one of five Jβ regions and the corresponding Cβ1 or Cβ2 regions; (b) “D‐J‐C clones” composed of Dβ1/or Dβ2/Jβ rearranged sequences and Cβ1 or Cβ2 sequences; (c) “5′C clones” made up of Cβ1 or Cβ2 regions preceded by the corresponding genomic 5′ flanking region. The presence of recombination signal sequences in J‐C and D‐J‐C clones suggests that the first derive from mRNA transcribed from promoters located in the 5′ J region and the second from mRNA transcribed from promoters situated in the 5′ D region. Nucleotide sequence analysis demonstrated that only three of the ten types of clones isolated had the potential to code a short cytoplasmic Tβ protein with a variable D‐Jβ N terminus. These findings have implications for the mechanisms of Tβ germ‐line transcription and the function of the Tβ transcripts.
The nature and importance of the inter‐ε chain disulfide bonds in human IgE
Authors: Helm Birgit A. , Ling Yan , Teale Catherine , Padlan Eduardo A. , Brüggemann Marianne 
Published: March 2007

AbstractIgE antibodies are best known for their pathological role in allergy. The class‐specific effector sites are located in the ε chains; these form covalent dimers via two cystine residues (Cys241 and Cys328) linking opposite Cε2 domains. The nature and biological significance of the inter‐ε chain disulfide‐bond arrangement is unresolved. For structural and functional analysis site‐specific mutations were introduced into the Cε2 domain of recombinant human IgE. The introduction of an additional cyanogen bromide cleavage site (His246 → Met) facilitated the identification of parallel disulfide bond pairing. This linkage was also confirmed for myeloma IgE PS by sequence determination of disulfide‐linked C2 dimers. Substitution of Cys241 and Cys328 by Ser does not destroy receptor binding, but reductive alkylation, or the replacement of Cys328 by Met, leads to loss of activity. This shows that covalent dimerization is not essential for IgE/receptor interaction and points to the importance of the structural integrity of the site surrounding Cys328, visualized in a new model of human Fcε.
Induction of antibodies against a peptide hapten does not require covalent linkage between the hapten and a class II presentable T helper peptide
Authors: Sarobe Pablo , Lasarte Juan‐José , Golvano José , Gullón Arturo , Civeira Maria‐Pilar , Prieto Jesús , Borrás‐Cuesta Francisco 
Published: March 2007

AbstractFollowing immunization with a complex antigen, a B cell internalizes this antigen through an interaction between its surface immunoglobulins and an epitope of the antigen. Enzymatic processing of the antigen frees one or more short peptide determinants (TD) which bind to class II molecules of the B cell. If the complex TD‐MHC II is recognized by the receptor of a T helper cell, T cell help is provided leading to the expansion of an antibody‐producing B cell clone specific for the epitope. We present experimental evidence proving that the induction of anti‐peptide hapten antibodies does not require covalent linkage between the peptide hapten and the peptide behaving as TD. Indeed, high anti‐peptide hapten antibody titers are induced if an emulsion of TD and hapten are injected in the same immunization site. This result suggests a way to manipulate antibody production with useful applications to research and therapy.
2,4,6‐Trinitrophenyl (TNP) responsiveness of anti‐TNP (Sp6) transgenic mice
Authors: Zöller Morgot 
Published: March 2007

AbstractTransgenic mouse models have demonstrated clonal deletion as well as clonal anergy of monospecific, high‐avidity autoreactive B cell. The function and fate of naturally activated B cells, many of them displaying degenerate specificity including autoreactivity, are still a matter of debate. The question was pursued in Sp6‐transgenic mice. Sp6, a monoclonal anti‐2,4,6‐trinitrophenyl (TNP) IgM has been shown to react with a variety of self antigens. Responsiveness of antibody‐secreting B cells was followed throughout postnatal development of Sp6‐transgenic mice and was related to the availability of antigen‐ and idiotype‐specific help.Thymus as well as spleen cells of transgenic mice contained a significantly higher number of TNP‐specific B cell than non‐transgenic controls. In contrast to control mice, the number of TNP‐specific B cells remained unchanged or decreased in thymus and spleen of transgenic mice after antigenic stimulation with TNP in T‐dependent (TD) and T‐independent (TI) form.Since the relative frequency of transgenic B cells was in particular diminished after repeated stimulation with TD antigen, it was examined whether limited responsiveness was linked to the available repertoire of helper T cells. Early after birth of transgenic individuals, thymic as well as splenic T cells which proliferated in response to TNP and Sp6 and provided help for B cells were found to be significantly augmented. Their number decreased rapidly during postnatal maturation and Th cells did not expand after antigenic stimulation. There was no indication that in the naive host transgenic B cells would suppress proliferation of TNP‐ and Sp6‐specific T cells, but they did so after antigenic stimulation. Furthermore, and in contrast to B cells of non‐transgenic mice, transgenic B cells were unable to present nominal antigen in a stimulatory way.The decrease in the number of B cells after antigenic stimulation indicated that autoreactive transgenic B cells may be subject to (functional) deletion under selected circumstances. In addition, idiotype‐ and antigen‐specific help was impaired in Sp6‐transgenic mice and this clearly was due to interactions with B cells expressing the immunoglobulin transgene.
Cloning and structural analysis of MMCP‐1, MMCP‐4 and MMCP‐5, three mouse mast cell‐specific serine proteases
Authors: Huang Ranyang , Blom Thomas , Hellman Lars 
Published: March 2007

AbstractHere we present the cloning of three novel mouse mast cell‐specific serine proteases, MMCP‐1, MMCP‐4 and MMCP‐5. A region of approximately 4 kb covering the five exons and 930 bp 5′ and 280 bp 3′ flanking sequences of the gene for MMCP‐1 was characterized by nucleotide sequence analysis. A comparison with the corresponding region of the rat mucosal mast cell‐specific protease RMCP‐II is presented. cDNA clones for the mast cell proteases MMCP‐4 (950 bp) and MMCP‐5 (1098 bp) were isolated from a cDNA library of a connective tissue mast cell‐like mouse mastocytoma cell line. All three proteases were found to belong to the family of chymotrypic serine proteases as deduced from the absence of the Asp 189 which is characteristic for all serine proteases having cleavage specificities similar to pancreatic trypsin. The active polypeptides, excluding possible post‐translational glycosylations, have an Mr of 25–26 kDa. Analysis of the amino acid composition reveals a positive net charge for all three proteases (MMCP‐1 +3, MMCP‐4 +18 and MMCP‐5 +12). Based on their high sequence identity (88%) and high positive net charges (+18 and +18, respectively) we assume that the MMCP‐4 is the mouse homolog to rat RMCP‐I.Probes specific for each of these three highly homologous protease genes have been generated by subcloning of fragments of approximately 100 bp in length, originating from the 3′ ends of the mRNA into plasmid vectors. Northern blot analysis of mRNA from a number of murine cell lines shows gene expression of these proteases to be specific for the differentiation stage of the mast cell. The MMCP‐1 is expressed only at the mucosal mast cell stage and and 5 only in mast cells of the connective tissue mast cell stage. These serine proteases may serve as highly specific markers in the analysis of mast cell heterogeneity, differentiation and function.
Immunodeficiency with low expression of the T cell receptor/CD3 complex. Effect on T lymphocyte activation
Authors: Le Deist Françoise , Thoenes Gabriela , Corado José , Lisowska‐Grospierre Barbara , Fischer Alain 
Published: March 2007

AbstractWe report the consequences of low expression of the T cell receptor (TcR)/CD3 complex by T lymphocytes from a 4‐year‐old boy with a mild immunodeficiency. TcR/CD3 expression was found to be deficient on both resting and activated T cells, using both anti‐CD3 and anti‐TcR α/β monoclonal antibodies. As shown by immunofluorescence and immunoprecipitation studies, residual expression (corresponding to about 10% of normal) was detectable on resting and activated TcR α/β+ T cells. Other T cell membrane receptors were normally expressed. The functional consequences of this TcR/CD3 expression deficiency included an absence of T cell proliferation, interleukin 2 receptor expression and calcium flux following anti‐CD3 and anti‐CD2 antibody‐triggered T cell activation. Antigen (tetanus toxoid, Candida and allogeneic cell)‐induced proliferation was detectable. In contrast, cytotoxic T cell activity towards allogeneic cells was deficient. These findings shed light on the function of the TcR/CD3 complex and indicate that the expression of a limited number of TcR/CD3 receptors may be sufficient to trigger antigen‐specific T cell activation (and, possibly, differentiation) and that anti‐CD3 antibody‐induced T cell activation differs somewhat from antigen/major histocompatibility complex molecule‐induced activation. These results also confirm that the CD2 pathway of T cell activation is CD3 dependent.
Biochemical identification of a direct physical interaction between the CD4: p56lck and Ti(TcR)/CD3 complexes
Authors: Burgess Kristine E. , Odysseos Andreani D. , Zalvan Craig , Druker Brian J. , Anderson Paul , Schlossman Stuart F. , Rudde Christopher E. 
Published: March 2007

AbstractThe CD4 and CD8 antigens function in synergy with the TcR/CD3 complex in the generation of intracellular signals leading to T cell proliferation. The association of the protein‐tyrosine kinase p56lck with CD4 and CD8 provides a potential mechanism in the generation of intracellular signals. Several studies have shown that CD4 can co‐modulate with TcR/CD3 suggesting that these receptor complexes may associate on the surface of the T cell. Nevertheless, it has proven difficult to formally demonstrate a direct physical interaction between the CD4 and TcR/CD3 complexes using biochemical techniques. In this study, we have used the sensitivity of the in vitro kinase assay to show a direct physical linkage between the CD4: p56lck complex and various CD3 subunits. Immunoprecipitation of CD4 from cell lysates derived from the T lymphoblastoid line HPB‐ALL results in the co‐purification of p56lck with an additional polypeptide at 20 kDa. Re‐precipitation analysis and isoelectric focusing demonstrated that this band corresponds to the CD3ϵ chain. An alternative approach which involves the labeling of microsomal membranes with [γ−32P]ATP revealed the presence of CD3ϵ and ζ chains in anti‐CD4 immunoprecipitates. By contrast, we were unable to demonstrate the association of the CD4: p56lck and TcR/CD3 complex in resting peripheral blood lymphocytes. These data indicate that the CD4: p56lck and TcR/CD3 complexes have the ability to form stable complexes on the surface of certain T cell lines.
Effect of aging on the autoimmune response to rat male accessory glands: deficit of I‐E‐positive peritoneal cells capable of inducing suppression
Authors: Pistoresi‐Palencia Maria C. , Romero‐Piffiguer Marta , Ferro Maria Elena 
Published: March 2007

AbstractThe present report analyzes the ability to induce suppression to rat male accessory gland (RAG) autoantigens and the characteristics of T suppressor (Ts)‐inducer peritoneal cells (PC) in old rats which show increased autoimmune responses. The injection of young rats with a purified fraction (FI) of RAG 10 and 3 days prior to immunization with chemically modified RAG (MRAG) markedly reduced the immune response to RAG autoantigens when compared with young rats which had only been immunized (controls), while the pretreatment of old rats did not block the delayed‐type hypersensitivity reaction to MRAG when compared with control old rats.The study of cell surface markers on PC from rats injected i.p. 2 h previously with FI of RAG (FI‐PC) showed an increase of OX‐6 (I‐A) and a decrease of OX‐17 (I‐E) in FI‐PC of old rats with respect to FI‐PC of young animals, which showed a selective increase of I‐E+ Ts‐inducer PC. The i.p. injection of FI‐PC from old rats into young recipients, 10 and 3 days prior to immunization with MRAG in complete Freund's adjuvant, did not modify the autoimmune response when compared with controls. By contrast, the injection of young and old rats with FI‐PC from young animals induced a significant suppression of the autoimmune response.The reduced percentage of I‐E+ suppressor‐inducer PC provides an explanation for the diminished ability to induce suppression to RAG autoantigens in old rats.