bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co‐crosslinking FcϵRII/CD23 and B cell surface immunoglobulin modulates B cell activation
Authors: Campbell Kim A. , Lees Andrew , Finkelman Fred D. , Conrad Daniel H. 
Published: March 2007

AbstractPrevious studies have shown that a highly multivalent from of anti‐IgD or anti‐IgM, prepared by conjugating the respective antibodies to dextran, causes extensive B cell proliferation with ng/ml concentrations of the anti‐immunoglobulin (Ig). A modification of this system has been exploited to investigate the effect of co‐crosslinking the FcϵRII and surface Ig by binding DNP to the dextran backbone (DNP‐dextran) and employing a DNP‐specific monoclonal IgE of either rat or mouse origin. Addition of anti‐IgD‐(Hδa/1)[DNP‐dextran] or anti‐IgM‐[DNP‐dextran] to purified, resting murine B cells resulted in B cell proliferation over a broad dose (0.03‐30 μg/ml). Addition of DNP‐specific rat or mouse IgE dramatically modulated the proliferative response. Proliferation in response to doses greater than 0.3 μg/ml Hδa/1‐[DNP‐dextran] was consistently reduced in a dose‐dependent manner in the presence of increasing amounts of IgE while proliferation to lower concentrations of Hδa/1‐[DNP‐dextran] was slightly enhanced or not influenced at all by the IgE anti‐DNP. Interleukin‐4 (IL‐4) significantly increased the IgE effect, in line with its known enhancing effects on FcϵRII levels. Experiments measuring Ig production rather than proliferation demonstrated that in the presence of IgE anti‐DNP, B cells produced lower amounts of immunoglobulin (IgG1 or IgM) in response to an anti‐Ig signal. Control experiments demonstrated that the IgE effect on proliferation was blocked by monoclonal anti‐FcϵRII, but not anti‐FcγRII, thus demonstrating the necessity for IgE/FcϵRII interaction. In addition, the necessity for co‐crosslinking was shown by the inability of IgE anti‐DNP to affect the proliferative response to Hδa/1‐dextran even in the presence of various doses of DNP‐dextran. These results demonstrate that co‐crosslinking of sIg and the FcϵRII results in an altered B cell response to anti‐Ig mediated activation. IL‐4 does not ablate this inhibition, in contrast to the effect of co‐crosslinking FcγRII and surface Ig, suggesting a model whereby IgE can modulate its own production.
A survey of protein‐DNA interaction sites within the murine immunoglobulin heavy chain locus reveals a particularly complex pattern around the DQ52 element
Authors: Kottmann Andreas H. , Brack Christine , Eibel Hermann , Köhler Georges 
Published: March 2007

AbstractThe expression of immunoglobulin (Ig) genes is regulated at two levels: rearrangement of individual gene segments and transcription of continuous genes. To find transacting factors involved in mediating locus‐ and segment specific gene activation and expression, we surveyed a 3600‐bp genomic region of the murine Ig heavy chain locus, spanning from the DQ52 element to the Ig heavy chain intron enhancer. We discovered nine, previously undescribed, protein‐DNA complexes and estimated their individual binding affinity preferences (Kr) by quantitative gel shift measurements. We observed one novel protein DNA interaction at the enhancer, two in the JH1 region and six within a 300‐bp region immediately 5′ to the DQ52 locus. The latter show a complex and specific binding pattern when comparing nuclear extracts derived from pre‐B cells and fibroblasts. Further characterization of the interactions at the DQ52 locus by electron microscopy revealed the preferential formation of a protein complex binding to the DQ52 locus with pre B cell extracts. This behavior and the clustering of interaction sites 5′ to the DQ52 element suggest that this region is involved in the regulation of heavy chain gene assembly.
T and B cell receptors discriminate major histocompatibility complex class II conformations influenced by the invariant chain
Authors: Rath Satyajit , Lin Rong‐Hwa , Rudensky Alexander , Janeway Charles A. 
Published: March 2007

AbstractDirect recognition of major histocompatibility complex (MHC) molecules may occur when T cells are positively selected in the thymus and also during recognition of non‐self MHC molecules. Since peptide recognition and binding of particular monoclonal antibodies is strongly influenced by the invariant chain (Ii) of the class II molecule, we have asked whether Ii also affects recognition of non‐self MHC molecules by T cells. We find that Ii binding alters MHC class II conformation as detected by a monoclonal antibody, and that this alteration is retained in cell surface MHC class II molecules after Ii dissociates. This altered conformation also affects recognition by allogeneic T cells. Normal T cells and T cell clones preferentially recognize MHC class II molecules that have been associated with Ii, suggesting that thymic selection may be influenced by MHC conformation independently of specific peptide binding.
Human genomic sequences corresponding to murine CD3η‐related transcripts: Lack of conservation or expression of homologous human products
Authors: Lerner Adam , Diener Andrew C. , Reinherz Ellis L. , Clayton Linda K. 
Published: March 2007

AbstractWe have cloned and sequenced human genomic DNA homologous to exons 9 and 10 of the CD3 ζ/η/θ locus. Although there are open reading frames within the human sequences corresponding to the translated portions of murine exons 9 and 10, we find no evidence of conservation of the encoded polypeptide product. Furthermore, using oligonucleotides derived from these homologous sequences, we are unable to detect human CD3η‐ or CD3θ‐like transcripts by polymerase chain reaction amplification of reverse‐transcribed RNA from a variety of human lymphoid tissues. Despite the absence of evidence for conservation of human CD3η and CD3θ, there is a surprising degree of similarity between human and murine nucleotide sequences, not only for exons 9 and 10 (78% and 70%, respectively), but also for the 9/10 intron (71%). A possible mechanism for this conservation is discussed.
Correlation between killing activity towards the murine L929 cell line and expression of membrane‐associated lymphotoxin‐related molecule of human lymphokine‐activated killer cells
Authors: Miyake Masazumi , Horiuchi Atsushi , Kimura Katsuhiko , Abe Yasuhito , Kimura Shigeru , Hitsumoto Yasuo 
Published: March 2007

AbstractHuman lymphokine‐activated killer (LAK) cells expressed a membraneassociated lymphotoxin‐related molecule (mLT) which was detected by flow cytometric analysis with anti‐lymphotoxin antibody. Upon removal of exogenous interleukin‐2 from LAK cell culture medium and another 24 h cultivation, the expression of mLT was decreased. Corresponding to the decrease of mLT expression, the killing activity of LAK cells towards L929 cells was remarkably reduced and killing of MIA PaCa‐2 and U937 cells was moderately reduced, whereas killing of Daudi and K562 cells was fully restored. The supernatant of mLT‐expressing LAK cells had no cytotoxic activity towards L929 cells in the absence of actinomycin D. Moreover, not only the killing of L929 cells but also that of human tumor cell lines (MIA PaCa‐2, U937) by mLT‐expressing LAK cells was partially inhibited in the presence of anti‐lymphotoxin antibody. These results suggest an involvement of mLT in the killing of some tumor target cells by LAK cells.
Restricted α/β receptor gene usage of idiotype‐specific major histocompatibility complex‐restricted T cells: Selection for CDR3‐related sequences
Authors: Snodgrass H. Ralph , Fisher Anne M. , Bruyns Eddy , Bogen Bjarne 
Published: March 2007

AbstractWe have sequenced the T cell receptor (TcR) Vα and Vβ genes of seven independent BALB/c CD4+ T cell clones specific for the immunoglobulin λ2 light chain produced by the MOPC 315 myeloma (λ2315). All the clones recognize a peptide of residues 91–101 of λ2315 and are restricted by the major histocompatibility complex (MHC) molecule I‐Ed. The results indicate that in BALB/c mice, this anti‐idiotypic response uses a very limited number of TcR. The four clones which cross‐react between Phe94 and Tyr94 peptide analogues use very similar receptors (Vα3, Jα1, Vβ6, Jβ1.1). The Vα3 gene used by all of these clones is identical and has not been previously described. Although the four clones differ in nucleotide sequence in the V/J borders, two had identical receptors at the amino acid level. One of the cross‐reactive clones exhibits a heteroclitic response to the Tyr94 peptide variant resulting from a single amino acid exchange in the V/J junction of the α chain. The three remaining clones which recognize only the Phe94 and not the Tyr94 peptide have somewhat more diverse TcR, however, two of these three clones use Vβ6. One of these non‐crossreacting clones is alloreactive, the specificity of which can be attributed to differences in the N‐D‐J sequences. Taken together these data indicate that this T cell response to an immunoglobulin idiotope is very restricted in terms of the TcR used. These data in conjunction with recently published results indicate that, although there can be strong preference for individual Vα or Vβ gene segments, certain Vα/Vβ combinations are preferentially selected for interacting with a given peptide/MHC combination, and that the CDR3‐related regions are crucial for antigen fine specificity and alloreactivity.
Synergistic induction of interleukin‐6 by tumor necrosis factor and lithium chloride in mice: Possible role in the triggering and exacerbation of psoriasis by lithium treatment
Authors: Beyaert Rudi , Schulze‐Osthoff Klaus , Van Roy Frans , Fiers Walter 
Published: March 2007

AbstractOne of the side effects of treatment of manic depressive disease with lithium salts is the triggering or aggravation of psoriasis. In a murine model, subcutaneous (s.c.) injection of a combination of tumor necrosis factor (TNF) and lithium chloride (LiCl) induces a psoriasiform inflammatory reaction. Recent studies suggest that interleukin (IL)−6 and its inducer TNF may play an important role in the pathophysiology of psoriasis. To understand the mechanism involved in the exacerbation of psoriasis by lithium salts, the IL‐1, IL‐6 and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) levels in murine skin injected with TNF in combination with LiCl were studied. IL‐6 levels in skin extracts of mice treated s.c. with a combination of TNF and LiCl were considerably increased as compared to the levels found in skin extracts from mice treated with TNF or LiCl alone. In contrast, in the same skin extracts IL‐1 levels were not changed and GM‐CSF was even not detectable. Although less pronounced, increased IL‐6 levels could also be found in the sera of mice treated s.c. with TNF and LiCl. Injection with IL‐1, interferon‐γ, lipopolysaccharide, or phorbol 12‐myristate 13‐acetate also induced IL‐6 in murine skin. However, these IL‐6 levels were not enhanced by co‐treatment with LiCl. Likewise, no inflammatory reaction could be seen in mice treated with these agents. These results suggest a role for endogenous TNF and IL‐6 in the triggering or aggravation of psoriasis in lithium‐treated patients.
Commitment to the T cell receptor‐αβ or ‐γδ lineages can occur just prior to the onset of CD4 and CD8 expression among immature thymocytes
Authors: Petri Howard T. , Scollay Roland , Shortman Ken 
Published: March 2007

AbstractTwo types of T lymphocytes, distinguishable by their surface expression of either the γδ or the αβ T cell receptor (TcR) for antigen, populate the periphery in the adult. In addition, immature precursors of both T cell types can be found in the thymus. While it is generally accepted that these two cell types represent distinct lineages, it is not known at which developmental stage these lineages diverge. The most mature thymocyte precursor population not yet expressing T lineage‐specific surface markers (i.e. CD3, CD4, and CD8) is known to be capable of generating TcR‐αβ T cells, and has been thought to be preprogrammed into the TcR‐αβ lineage at an earlier developmental stage. We now show that this late‐stage precursor is capable of giving rise to cells of both the TcR‐αβ and ‐γδ lineages, both in vitro after intrathymic transplantation, and in vitro in simple culture medium or medium with cytokines. Thus it appears that the divergence of TcR‐αβ and ‐γδ cells can occur at a relatively late stage of intrathymic development, just prior to the onset of CD4 and CD8 expression in most cells.
Random entry of circulating lymphocyte subsets into peripheral lymph nodes and Peyer's patches: No evidence in vivo of a tissue‐specific migration of B and T lymphocytes at the level of high endothelial venules
Authors: Westermann Jürgen , Blaschke Volker , Zimmermann Gesine , Hirschfeld Ulrich , Pabst Reinhard 
Published: March 2007

AbstractLymphocytes continuously migrate through the body and thus immune competent cells are constantly delivered to most tissues. They interact with high endothelial venules (HEV) via specific homing receptors and vascular addressins, and these molecules seem to be the reason for a preferential homing of B lymphocytes into Peyer's patches and of T lymphocytes into peripheral lymph nodes.When lymphocytes derived from lymph node cell suspensions were applied in the in vitro lymphocyte/endothelium binding assay, the well‐known preference of mouse lymph node B lymphocytes for Peyer's patch HEV compared to peripheral lymph node HEV was confirmed in the rat (2.8 times). When in the same in vitro assay thoracic duct lymphocytes (TDL) were used this preference was far less obvious (1.4 times). However, by injecting rat TDL intravenously and by tracing them directly in HEV, B, T, CD4+ and CD8+ lymphocytes are seen to enter Peyer's patches and peripheral lymph nodes in vivo without preference.Thus, in contrast to lymphocytes from lymph node cell suspensions, no evidence was found of a tissue‐specific migration of thoracic duct B, T, CD4+ and CD8+ lymphocytes at the HEV level. This finding demonstrates the importance of considering both experimental conditions and the cell source used when investigating lymphocyte traffic.
Production of 17.2.25 μ transgenic and endogenous immunoglobulin in X‐linked immune deficient mice
Authors: Rabin Evelyn , Yingzi Cong , Imanishi‐Kari Thereza , Wortis Henry H. 
Published: March 2007

AbstractIn M54 mice transgenic for a completely rearranged μa heavy chain there is a decrease in total B cells and the rearrangement of endogenous immunoglobulin genes is partially inhibited. Surprisingly, however, endogenous immunoglobulin gene rearrangement and significant heavy chain polypeptide production does occur. We tested the hypothesis that only CD5+ B cells produce endogenous immunoglobulin by taking advantage of the fact that X‐linked immune deficient (xid) mice normally are deficient in CD5+ B cells. We found that the frequency of CD5+ splenic B cells was similar in XxidY transgenic and non‐transgenic F1 males, and in XxidX transgenic and non‐transgenic F1 females. In both XxidX and XxidY transgenic F1 mice some, but not all, splenic B cells are CD11b+. There was a striking deficit of splenic B cells expressing endogenous immunoglobulin in XxidY transgenic mice, although this was not true for peritoneal cells. Thus, the introduction of the 17.2.25 μ transgene does not prevent the development of CD5− B cells nor does it limit endogenous immunoglobulin gene arrangement and expression solely to CD5+ B cells. However, in mice capable of expressing B cell surface CD5 or CD11 this transgene can lead to expansion of the fraction of B cells positive for these molecules. We conclude that while the introduction of the 17.2.25 μ transgene alters the frequencies of B cell populations maturation is not limited to one subpopulation.
Functional maturation of recent thymic emigrants in the periphery: Development of alloreactivity correlates with the cyclic expression of CD45RC isoforms
Authors: Yang Chun‐Ping , Bell Eric B. 
Published: March 2007

AbstractThe transition from fully developed CD4+CD8− single‐positive (SP) thymocytes into fully mature recirculating peripheral T cells is both poorly understood with regard to the expression of restricted isoforms (CD45R) of the leukocyte common antigen and in terms of T cell function. The present investigation monitored the extrathymic development of CD4+CD8− SP thymocytes in euthymic recipients using allotype‐marked donor cells and monoclonal antibody OX22 which recognizes an epitope on the C exon of rat CD45R. We established that donor‐derived cells in the blood 1 day later bore the phenotype of the injected SP thymocytes (CD4+ Thy‐1+ CD45RC−). T cells with the identical phenotype were also present in the thoracic duct lymph of uninjected rats, suggesting that the Thy‐1+ CD45RC− T cells represent recent thymic emigrants (RTE) which have migrated to the periphery of their own accord. During extrathymic maturation donor‐derived peripheral RTE lost Thy‐1 within 3 days and expressed the CD45RC+ high molecular weight isoform by day 7; between days 8 and 14 a proportion (25%–30%) of the donor cells once again lost the high molecular weight isoform (CD45RC−). The transition of SP (CD45RC−) thymocytes to fully mature CD45RC+ CD4 T cells via intermediate peripheral RTE was accompanied at each stage by an increased ability of the maturing T cells to induce skin allograft rejection. Unexpectedly, the subsequent loss of the high molecular weight isoform, following presumed antigen encounter, was associated with a significant reduction in the ability of this Thy‐1− CD45RC− subpopulation to effect graft rejection. The cyclic expression of CD45RC isoforms on both immature and mature CD4 T cells and the fact that the low molecular weight isoform was found in the periphery on both RTE (unquestionably naive) and antigen‐experienced CD4 T cells, makes it unlikely that this isoform uniquely identifies memory T cells, at least in the rat.
Cytokines inhibit the development of liver schizonts of the malaria parasite plasmodium berghei in vivo
Authors: Vreden Stephen G. S. , Van den Broek Maries F. , Oettinger Maria C. , Verhave Jan Peter , Meuwissen Joep H. E. T. , Sauerwein Robert W. 
Published: March 2007

AbstractThe effect of induction of an acute‐phase response and its mediators on the development of liver schizonts of the rodent malaria parasite Plasmodium berghei was investigated in Brown Norway rats. Subcutaneous injection of turpentine oil 24 h or 5 min before inoculation of sporozoites resulted in 80% and 35% reduction of schizont development, respectively. Turpentine oil induced high plasma levels of interleukin‐6 (IL‐6). Intraperitoneal administration of IL‐1, IL‐6 or both, significantly reduced liver schizont development. This reduction was also present if IL‐6 had been administered 24 h after sporozoite inoculation. Inhibition induced by IL‐1 could be prevented by simultaneous administration of polyclonal anti‐IL‐6. Administration of polyclonal anti‐IL‐6 without IL‐1 resulted in a 40% increase of liver schizonts compared to control animals. We conclude that induction of an acute‐phase response during experimental Plasmodium berghei infections in Brown Norway rats, strongly inhibits liver schizont development and that IL‐6 is a key mediator in this process.
The adjuvant effect of Vibrio cholerae and Escherichia coli heat‐labile enterotoxins is linked to their ADP‐ribosyltransferase activity
Authors: Lycke Nils , Tsuji Takao , Holmgren Jan 
Published: March 2007

AbstractThis study addressed the question of whether the mucosal adjuvant property of cholera toxin (CT) and the structurally closely related Escherichia coli heat‐labile toxin (LT) requires the enterotoxic and adenylate cyclase/cAMP activating property of these molecules. Therefore, we investigated the cytotoxic and adjuvant abilities of the enterotoxins and compared the results with those obtained with the non‐toxic CT and LT derivatives; recombinant CTB (rCTB) and a mutated LT (mLT), which had a single amino acid substitution in position 112 (Glu→Lys) of the A subunit. Detailed functional studies revealed that, in contrast to the enterotoxins, both rCTB and mLT lacked ADP‐ribosylating and cAMP‐stimulating abilities. However, similar membrane ganglioside GM1‐receptor binding ability of all the putative adjuvants was demonstrated. When the probe antigen, keyhole limpet hemocyanin (KLH), was given perorally together with CT or LT strong gut mucosal anti‐KLH immune responses were stimulated, whereas no or very low anti‐KLH responses were seen in the groups which antigen admixed with rCTB or the mLT. Moreover, the specific serum antibody responses to the various immunization protocols closely paralleled the local anti‐KLH response in the gut. From these results it appears that the adjuvant mechanism of LT, and probably also of CT, is linked to the ability to ADP‐ribosylate and to stimulate cAMP formation. However, this study does not unequivocally rule out other possibilities such as interactions by the A1 fragment of CT or LT with other G‐proteins than Gsα or events that parallel or precede the effects on the adenylate cyclase/cAMP system. Thus, the levels of ADP‐ribosylation and cAMP‐induction that are required and the key event or target cell that is responsible for the adjuvant effect of CT and LT remain to be elucidated. Studies are underway to address these issues.
Tyrosine kinase triggering in thymocytes undergoing positive selection
Authors: Carrera Ana C. , Baker Carrie , Robert Thomas M. , Pardoll Drew M. 
Published: March 2007

AbstractDeveloping T cells undergo distinct selection processes that determine the T cell receptor (TcR) repertoire. One of these processes is positive selection. Positive selection involves the differentiation to mature T cells of thymocytes bearing TcR capable of recognizing antigens in the context of self‐major histocompatibility complex (MHC) molecules. To study the potential involvement of tyrosine phosphorylation in the mechanism of positive selection, we have analyzed the activities of the tyrosine kinases pp56lck and pp59fyn in thymocytes expressing a unique TcR specific for HY antigen+ H‐2 Db. Thymocytes undergoing positive selection displayed higher kinase specific activities of pp56lck and pp59fyn than nonselecting thymocytes. Furthermore, these increases in kinase activities were found only in the CD4+CD8+ subpopulation of thymocytes, where the selection process is believed to occur. These data suggest that tyrosine phosphorylation is part of the intracellular signals involved in MHC class I‐driven positive selection from CD4+CD8+ immature thymocytes to CD4−CD8+ mature cells.