bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preferrential rearrangement in normal rabbits of the 3′ VHa allotype gene that is deleted in Alicia mutants; somatic hypermutation/conversion may play a major role in generating the heterogeneity of rabbit heavy chain variable region sequences
Authors: Allegrucci Massimo , Young‐Cooper Glendowlyn O. , Alexander Cornelius B. , Newman Barbara A. , Mage Rose G. 
Published: March 2007

AbstractThe rabbit is unique in having well‐defined allotypes in the variable region of the heavy chain. Products of the VHa locus, (with alleles al, a2, and a3), account for the majority of the serum immunoglobulins. A small percentage of the serum immunoglobulins are a‐negative. In 1986, Kelus and Weiss described a mutation that depressed the expression of the Ig VH a2 genes in an a1/a2 rabbit. From this animal the Alicia rabbit strain was developed and the mutation was termed ali. We previously showed, using Southern analysis and the transverse alternating field electrophoresis technique, that the difference between the ali rabbit and normal is a relatively small deletion including some of the most 3′ VH genes. The most JH proximal 3′ VH1 genes in DNA from normal rabbits of a1, a2 and a3 haplotypes encode a1, a2 and a3 molecules respectively, and it has been suggested that these genes are responsible for allelic inheritance of VHa allotypes. The present study suggests that the 3′ end of the VH locus probably plays a key role in regulation of VH gene expression in rabbits because VH gene(s) in this region are the target(s) of preferential VDJ rearrangements. This raises the possibility that mechanisms such as somatic gene conversion and hypermutation are at work to generate the antibody repertoire in this species. Our data support the view that the 3′ VH1 gene may be the preferred target for rearrangement in normal rabbits, and for the normal chromosome in heterozygous ali animals. However, homozygous ali rabbits with a deletion that removed the a2‐encoding VH1 on both chromosomes do survive, rearrange other VH genes and produce normal levels of immunoglobulins as well as a significant percentage of B cells which bear the a2 allotype. This challenges the view that one VH gene, VH1, is solely responsible for the inheritance pattern of VHa allotypes.
Conserved V(D)J junctional sequence of cross‐reactive cytotoxic T cell receptor idiotype and the effect of a single amino acid substitution
Authors: Hirama Toshiyasu , Takeshita Sunao , Matsubayashi Yuji , Iwashiro Michihiro , Masuda Tohru , Kuribayashi Kagemasa , Yoshida Yataroh , Yamagishi Hideo 
Published: March 2007

AbstractA dominant T cell population bearing the cross‐reactive idiotype of T cell antigen receptor (TcR) has been obtained using an anti‐TcR monoclonal antibody (mAb) developed in syngeneic mice. Forty‐four cytotoxic T cell (CTL) clones with reactivity to a mAb (N9 127) were selected out of 396 H‐2Db‐restricted CTL clones specific for FBL‐3 tumor antigen from C57BL/6 mice. These CTL clones were divided into two groups according to the blocking pattern of cytotoxic activities with mAb N9‐127. All eight CTL clones chosen from both groups expressed TcR with a specific combination of α and β chains (Vα1Jα112‐2/Vβ10Dβ2.1Jβ2.7), and the difference in the blocking susceptibility resided in a single amino acid substitution (Gly to Asp) in the D‐J joint of β chain. This provides direct evidence for the molecular basis of cross‐reactive idiotypes of TcR recognized by mAb.
Inhibition of B cell proliferation with anti‐CD19 monoclonal antibodies: anti‐CD19 antibodies do not interfere with early signaling events triggered by anti‐IgM or interleukin 4
Authors: Rigley Kevin P. , Callard Robin E. 
Published: March 2007

AbstractThe 95‐kDa antigen recognized by the anti‐CD19 panel of monoclonal antibodies is found on the surface of most cells of the B cell lineage. Anti‐CD19 antibodies inhibit B cell proliferation in response to anti‐Ig plus interleukin 4 (IL4), but enhance the response to mitogenic concentrations of either phorbol 12‐myristate 13‐acetate (PMA) or Epstein‐Barr virus. This dichotomy in the effect of anti‐CD19 antibodies suggested that the inhibitory action may be directed at the transmembrane signaling pathways utilized by anti‐IgM and IL4. To investigate this hypothesis, an attempt was made to determine the mechanism of signal transduction utilized by the CD19 antigen, and elucidate its effect on transmembrane signaling invoked by anti‐immunoglobulin and IL4. Binding of anti‐CD19 antibody to B cells did not promote activation of either the phosphoinositide or cAMP signaling pathways. In addition, anti‐CD19 antibody did not inhibit phosphatidylinositol bisphosphate (PIP2) hydrolysis induced by anti‐IgM or IL4, nor did it interfere with cAMP induction by IL4. We also found that anti‐CD19 antibody inhibited PMA plus calcium ionophore‐induced B cell proliferation. This evidence indicates that anti‐CD19 mAb interrupts the signaling cascade at a point distal to receptor‐mediated breakdown of PIP2 and/or activation of adenyl cyclase. This conclusion was fully consistent with experiments in which anti‐CD19 antibody was shown to inhibit DNA but not RNA synthesis, and the observation that anti‐CD19 antibody must be present between 6 h and 20 h after the initiation of the culture suggesting that anti‐CD19 mAb exerts its inhibitory effect in late G0 or G1, after the initial signaling events.
Immunobiological studies on experimental visceral leishmaniasis I. Changes in lymphoid organs and their possible role in pathogenesis
Authors: Saha Bhaskar , Nanda‐Roy Heramba , Pakrashi Anita , Chakrabarti Rohini Nandan , Roy Syamal 
Published: March 2007

AbstractStudies were carried out to determine changes in lymphoid organs i. e. spleen, lymph node and bone marrow (BM) in progressive experimental visceral leishmaniasis. Mononuclear phagocytes in the BM were increased; spleens showed a hypercellularity coupled with a rise in parasite burden while secondary follicles with no apparent depletion of paracortex were seen in the lymph node. This enhanced proliferation of mononuclear phagocytes in the BM and probably their subsequent recruitment in the spleen could be induced in naive recipients by injecting nylon wool‐purified lymph node cells derived from infected mice together with sonicated leishmanial antigen(s). Similar changes could also be induced in the BM of naive recipients by injecting serum of infected mice. In control experiments where both donor and recipients were uninfected such changes were not apparent. A working hypothesis is proposed to delineate the role of lymphoid organs in the pathogenesis of experimental visceral leishmaniasis.
Na+/H+ antiporter has different properties in human B lymphocytes according to CD5 expression and malignant phenotype
Authors: Gaidano Gianluca , Caligaris‐Cappio Federico , Treves Silvia , Bussolino Federico , Pescarmona Gianpiero , Ghigo Dario , Bosia Amalia 
Published: March 2007

AbstractIn B chronic lymphocytic leukemia (B‐CLL) cells, lipopolysaccharide (LPS) and phorbol esters fail to activate the plasma membrane‐associated Na+/H+ anti‐porter and, subsequently, to elicit a rise in cytosolic pH. Since these events are thought to be a prerequisite for LPS‐induced proliferation of B normal lymphocytes, we analyzed the kinetic properties of Na+/H+ antiporter in B‐CLL cells as compared to both CD5− and CD5+ normal B lymphocytes. In the present work we report that Na+/H+ exchange rate after acid loading is drastically decreased in B‐CLL cells, as compared to normal CD5− B lymphocytes, although the antiporter affinity for external Na+ and internal H+ is not significantly different in both cell populations. Kinetic data account for a reduction in the number of operating antiport units in B‐CLL. The Na+/H+ antiporter of CD5+ normal B lymphocytes exhibits both an exchange rate and an ion affinity significantly higher than that observed in both CD5+ B‐CLL cells and CD5− B normal lymphocytes, thus suggesting a possible explanation for their activated phenotype.
Complementary roles for CD2 and LFA‐1 adhesion pathways during T cell activation
Authors: Moingeon Philippe E. , Lucich Jeanne L. , Stebbins Christopher C. , Recny Michael A. , Wallner Barbara P. , Koyasu Shigeo , Reinherz Ellis L. 
Published: March 2007

AbstractThe influence of T cell receptor (TcR) triggering on T cell adhesion function has been systematically investigated in the present studies; we show that the adhesion function of LFA‐1 is minimal in non‐activated T cells but is augmented within minutes following TcR‐mediated activation. In contrast, CD2 function is essentially optimal in non‐activated T cells and undergoes no detectable modification within 12 h of TcR stimulation. Protein kinase C activation augments LFA‐1 but not CD2 adhesion function and cyclic AMP reduces LFA‐1 adhesion without affecting CD2‐LFA‐3 interactions. Up‐regulation of the LFA‐1 pathway occurs in the absence of any detectable surface redistribution of this molecule, suggesting an activation dependent modification leading to a high‐affinity ICAM‐1 binding state. The TcR independence of CD2 adhesion function implies a critical role of the CD2 pathway in initiating cell‐cell interactions prior to TcR engagement and LFA‐1‐ICAM‐1 binding and underscores the complementary nature of the CD2 and LFA‐1 adhesion pathways during the immune response.
Expression and biological effects of high levels of serum IgE in ϵ heavy chain transgenic mice
Authors: Adamczewski Martin , Köhler Georges , Lamers Marinus C. 
Published: March 2007

AbstractWe have generated and examined transgenic mice carrying a rearranged immunoglobulin transgene coding for the heavy chain of an IgE antibody. These mice produce the secreted form of the recombinant ϵ heavy chain. Serum IgE levels were increased at least 100‐fold over control values. Transgenic ϵ mRNA was detected in spleen and thymus, not in liver and heart. Transgenic ϵ production in vitro was slightly up‐regulated by T cells, but not affected by interleukin 4 in vitro or Nippostrongylus infestation in vivo. The B cell and T cell compartments and antigen‐specific IgE, IgG1 and IgM responses as well as the increase in endogenous IgE after Nippostrongylus infestation in transgenic mice were normal. These data indicate that the presence of high levels of transgenic IgE did not induce class‐specific suppressive mechanisms. Transgenic IgE bound to Fcϵ receptor type I and Fcϵ receptor type II and mediated histamine release from mast cells in vitro and an allergic skin reaction in vivo. It inhibited an ovalbumin‐specific skin reaction in ovalbumin‐immunized transgenic mice only during the initial phases of the immune response. This result has a bearing on the feasibility of immune therapy of allergic diseases with substances that block binding of IgE to its receptors.
The MRC OX‐47 antigen is a member of the immunoglobulin superfamily with an unusual transmembrane sequence
Authors: Fossum Sigbj⊘Rn , Mallett Susan , Neil Barclay A. 
Published: March 2007

AbstractThe MRC OX‐47 monoclonal antibody recognizes a membrane antigen present at low levels on many lymphocytes but whose expression is markedly increased on activation with mitogens. cDNA clones for the OX‐47 antigen were isolated from an expression library and the protein sequence deduced. It contains a leader sequence giving a mature protein of 251 amino acids with a single putative transmembrane region, a cytoplasmic domain of 40 amino acids and an extracellular domain of 187 amino acids that contained two immunoglobulin‐like domains. The putative transmembrane sequence includes a glutamic acid residue within the hydrophobic sequence. The presence of acidic residues within the hydrophobic sequence of transmembrane sequences usually indicates association with other polypeptides and this is predicted for the OX‐47 antigen. A sequence of 37 amino acids that included all the transmembrane region was identical to that of the chicken HT7 antigen present on endothelium in brain and erythroblasts. The level of protein sequence identity in the Ig‐like domains was lower but HT7 is almost certainly the chicken homologue of the rat OX‐47 antigen. The ligand and function of the molecule are unknown. In addition to lymphoblasts the OX‐47 antigen was localized on a variety of other cell types including various immature cells, endothelia and cells with excitable membranes.
T cell proliferation induced by monoclonal antibodies to a phosphatidylinositol‐linked differentiation antigen of guinea pig lymphocytes
Authors: Schäfer Hubert , Burger Reinhard , Scheper Rick J. , Healey Don G. , Schenkel Johannes 
Published: March 2007

AbstractMonoclonal antibodies (mAb) to differentiation antigens frequently influence the in vitro function of antigen‐bearing cells. We characterized a 32–36‐kDa membrane protein expressed on guinea pig lymphocytes and Langerhans cells. A series of independently derived mAb to this protein, now called guinea pig T cell activation antigen (gpTAA), induced strong proliferation of T cells in vitro. Cross‐linking of the mAb by a secondary antibody (rabbit anti‐mouse Ig) and costimulation with phorbol 12‐myristate 13‐acetate were required for activation. Treatment of the cells with phosphatidylinositol‐specific phospholipase C greatly reduced the amount of antigen expressed on the cell surface as measured by flow cytometry analysis. This finding indicates that the antigen is anchored to the cell membrane via phosphatidylinositol linkage as shown similarly for other membrane proteins with T cell activating properties, e.g. Thy‐1 and Ly‐6. The guina pig protein differs, however, in its molecular weight and tissue distribution from similar proteins identified in the mouse or in the rat system. Unlike Thy‐1, gpTAA is also expressed on B Lymphocytes and Langerhans cells. Considering the previously described involvement in cellular adhesion, and the functional characteristics reported here, gpTAA might represent a new species of differentiation antigen with T cell‐activating capacity.
Anti‐idiotypic antibodies to human anti‐gp120 antibodies bind recombinant and cellular human CD4
Authors: Corre Jean‐Philippe , Février Michèle , Thèze Jacques , Zouali Moncef , Chamaret Sophie 
Published: March 2007

AbstractThe presence of anti‐CD4 antibodies in sera of human immunodeficiency virus (HIV)‐seropositive individuals has been recently documented, but its origin remains unknown. To test the hypothesis that anti‐idiotypic antibodies to gp120, the HIV envelope glycoprotein with high affinity for CD4, mimic the configuration of gp120 and bind CD4, we performed two sets of experiments. First, we tested the possibility that anti‐CD4 antibodies present in sera of a proportion of HIV‐positive individuals exhibit variable region complementarity to autologous anti‐gp120 antibodies. We show here that affinity‐purified human anti‐gp160 antibodies recognize specifically autologous affinity‐purified anti‐CD4 antibodies. We also demonstrate that antibodies to CD4 competitively inhibit anti‐gp160 autologous antibodies binding to gp160. This implies that at least some anti‐CD4 antibodies are directed towards idiotypic motifs located on anti‐gp120 antibodies and that they may result from an anti‐idiotypic response to anti‐gp120 antibodies. In a second set of experiments, we examined the effect of anti‐idiotypic immunization of experimental animals against human anti‐gp120 antibodies. We found that anti‐idiotypic antibodies produced in a rabbit immunized against affinity‐purified human anti‐gp120 antibodies specifically recognize recombinant and cellular human CD4, and that this interaction is competitively inhibited by soluble CD4. The data support the concept of idiotypic mimicry whereby anti‐idiotypic antibodies produced against anti‐gp120 antibodies recognize CD4, the cellular receptor of HIV.
Molecular cloning of the cDNA coding for properdin, a positive regulator of the alternative pathway of human complement
Authors: Nolan Kathleen F. , Kaluz Stefan , Reid Kenneth B. M. , Dierich Manfred P. , Schwaeble Wilhelm 
Published: March 2007

AbstractNorthern blot analysis indicated that the mRNA for human properdin is approximately 1.5 kb long and that its level in U‐937 cells is increased by pretreating the cells with phorbol 12‐myristate 13‐acetate (PMA). Using a human genomic probe clones coding for human properdin were isolated from a λgt10 cDNA library derived from PMA‐treated U‐937 cells. The sequence of the 1474‐bp cDNA insert of the longest clone revealed an open reading frame of 1326 bp coding for the entire 442 amino acids of the mature form of human properdin and 67 bp coding for 22 amino acids of typical, but incomplete leader sequence. Polymerase chain reaction “RACE” experiments identified the start site ATG and revealed the complete, 27‐amino acid‐long, leader peptide sequence. Within the 81‐bp 3' non‐translated extension a polyadenylation signal was identified 41 bp downstream from the stop codon, TAA, and 12 bp upstream of a 19 nucleotide long poly(A) tail. The amino acid sequence of human properdin is clearly divided into three distinct regions: a 49 residue‐long N‐terminal region, a 32 residue‐long C‐terminal region and a middle region, covering residues 50 to 411, composed of six tandemly repeated thrompospondin repeat (TSR) motifs of the type first described in the adhesive glycoprotein thrombospondin and also known to be present in the C6, C7, C8α, C8β and C9 terminal components of complement. Human and mouse properdin sequences show a high (∼76%) degree of identity with almost complete conservation of the relatively large number of Cys (44) and Trp (20) residues.
Carbohydrate synthesis inhibitors decrease interleukin 1‐stimulated lymphocyte binding to endothelial cells
Authors: Renkonen Risto , Ustinov Jarkko 
Published: March 2007

AbstractLymphocyte extravasation (homing) is initiated when lymphocyte adheres to endothelial cells. All know protein structures involved in the lymphocyte binding located on the endothelial surface are heavily glycosylated. We asked therefore whether these carbohydrate motifs had a role in the lymphocyte homing. The relative importance of the N‐linked chains on biological effects mediated by glycoproteins can be studied with specific inhibitors of carbohydrate processing, i.e. 1‐deoxynojirimycin (DN), castonospermine (CAST), 1‐deoxymannojirimy‐cin (DMN) and swainsonine (SW), which produces different kinds of blocked carbohydrate chains. N‐linked carbohydrate chains are modified in the Golgi apparatus and in the final glycoprotein they can be either of high‐mannose‐, hybrid‐ or complex‐type motifs, having the same core structure but different terminal structures. We show here that when all N‐linked carbohydrates were cleaved off from the cell surface glycoproteins by treating endothelial cells with N‐glycosidase F interleukin 1‐induced lymphocyte binding was reduced almost to non‐stimulated control values. Treatment of endothelial cells with CAST led to generation of glycoproteins carrying high‐mannose‐type oligosaccharides, which are glucose capped with three glucose molecules on the chain. CAST treatment resulted in an 85% decrease in lymphocyte binding compared to interleukin 1‐induced levels. DMN treatment, resulting in accumulation of high‐mannose type oligosaccharides without any terminal glucoses on the cell surface, caused a similar inhibition of lymphocyte binding to that induced by CAST treatment. SW treatment, leading to accumulation of hybrid‐type glycoproteins, decreased only slightly the lymphocyte binding. These results suggest that carbohydrates indeed have a role in lymphocyte binding to endothelial cells.
Murine thymic nurse cell clone supports the growth of fetal thymocytes in the presence of interleukin 2
Authors: Doi Hideyuki , Nakagawa Satoshi , Hata Masahiro , Kasahara Shigeru , Itoh Tsunetoshi , Sakata Tsuneaki , Suzuki Ryuji , Nagata Kinya , Sugamura Kazuo , Nanno Masanobu 
Published: March 2007

AbstractTo investigate the role of thymic nurse cells (TNC) in activation and differentiation of fetal CD4−CD8− (double‐negative) thymocytes, we have co‐cultured murine fetal thymocytes (14–15 days of gestation) with an established murine TNC clone. We show here that TNC induced the growth of the fetal double‐negative thymocytes in the presence of recombinant interleukin 2 (rIL2). Activated fetal thymocytes markedly formed lymphocyte‐TNC complexes and proliferated extensively after 5 days in the co‐culture. The activated fetal thymocytes in this co‐culture condition remained double negative after 10 days in culture. None of them gave rise to phenotypically and functionally competent lymphocytes during this period. TNC alone and the supernatant of TNC had no effect on activation. The presence of both TNC and rIL2 was necessary for the growth of fetal thymocytes in our system. The proliferation of fetal thymocytes was inhibited by a monoclonal antibody against mouse IL2 receptors (IL2R). The fetal thymocytes could be maintained further in this co‐culture condition. The prolonged cultivation of fetal thymocytes resulted in the establishment of the fetal thymocyte line and its several clones. CD4 single‐positive cells of activated fetal thymocytes first appeared 14 days after the onset of culture and their number increased, whereas CD8+ cells or CD4CD8 double‐positive cells were not observed. These results indicate that fetal CD4−CD8− thymocytes underwent phenotypic change after long periods of culture. All established clones of fetal thymocytes are CD4 single positive showing lymphocyte‐TNC interactions but do not express CD3 complex. Northern blot analysis detected mRNA for the γ T cell receptor, but no messages for the δ, α or β T cell receptor. Chemical cross‐linking of 125I‐labeled IL2 revealed that the 90‐kDa band (presumably considered to be the IL2R β chain) was clearly present in IL2‐responsive fetal clones, whereas freshly isolated day 14–15 fetal thymocytes lacked the band.Taken together, TNC might be involved in the differentiation and /or expansion of murine fetal thymocytes by inducing IL2R β chain, which forms the functional IL2R together with IL2R α chain and CD4, one of the T cell accessory molecules, on the cell surface through direct cell‐cell interaction.
Pulmonary epithelial T cells induced by viral infection express T cell receptors α/β
Authors: Openshaw J. M. 
Published: March 2007

AbstractCells were recovered from the lungs of mice by bronchoalveolar lavage before and after infection with respiratory syncytial (RS) virus. Uninfected mice yielded mostly macrophages, but after RS virus infection lymphocytes also appeared. Recovered cells were stained for CD4, CD8 and either CD3, T cell receptor (TcR) α/β or TcR γ/δ and analyzed by 3‐color flow cytometry. Both the CD4+CD8− and CD4−CD8+ subpopulations stained uniformly for CD3 and TcR α/β, while none stained for TcR γ/δ. Of the CD4−CD8− cells, about 5% stained for CD3 and TcR α/β during the first week after infection, although this figure increased during the second week. A small and variable fraction of this subset stained for TcR γ/δ. These results oppose the view that lymphocytes expressing TcR γ/δ predominate in initial epithelial immune responses to viral infections.