bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immigration of thoracic duct B lymphocytes into established germinal centers in the rat
Authors: Vonderheide Robert H. , Hunt Simon V. 
Published: March 2007

AbstractImmigration of B lymphocytes into established germinal centers in the rat was studied by transferring genetically marked thoracic duct B cells to non‐irradiated congenic hosts at various times between 3 days before and 6 days after host immunization. Seven days after host immunization, the distribution of donor B cells to lymph node germinal centers (relative to their distribution to non‐germinal center lymph node areas) was measured by two‐color flow cytometry in which (a) donor and host B cells were distinguished by their Ig ϰ chain allotypes, and (b) germinal center B cells were distinguished by their lack of labeling with the monoclonal antibody HIS22. Thoracic duct B cells from long‐term antigen‐primed rats were found to immigrate into host germinal centers much better than B cells from unprimed donors. This effect was antigen specific: primed B cells only immigrated well into host germinal centers induced by the priming antigen. Although B cells localized in germinal centers most efficiently when injected before immunization, specifically primed donor B cells injected after immunization were still found to be at least as evenly distributed to germinal centers as to other lymph node areas, whereas unprimed B cells transferred after immunization localized poorly in host germinal centers. These findings are discussed in light of recent suggestions that memory B cell clones are maintained by continued antigenic stimulation within secondary lymphoid follicles.
The CD59 antigen is a structural homologue of murine Ly‐6 antigens but lacks interferon inducibility
Authors: Philbrick William M. , Palfree Roger G. E. , Maher Stephen E. , Bridgett Margot M. , Sirlin Sonia , Bothwell Alfred L. M. 
Published: March 2007

AbstractA cDNA encoding the human leukocyte antigen CD59 has been isolated from the erythroid cell line K‐562 and its identity confirmed through expression in COS cells. Northern blotting reveals three message species of approximately 800, 1400 and 2000 bases in size, which are constitutively expressed in all lymphoid, erythroid, myeloid, and neural cell types tested thus far. Southern blotting of human DNA indicates a pattern consistent with the presence of a single gene, which has been mapped to chromosome 11 by somatic cell hybrids. Also, the finding of a transcriptionally active cross‐hybridizing gene in monkey cells suggests conservation of CD59 sequences among primates. Comparison of the CD59 protein sequence with those of the Ly‐6E and Ly‐6C antigens discloses a similarity in overall structure, including the alignment of abundant cysteine residues, hydrophobic carboxy termini and conservation of amino acids surrounding the proposed phosphatidylinositol‐glycan modification site for Ly‐6 molecules. Unlike Ly‐6, however, CD59 expression does not appear to be inducible with interferons. This, along with its limited homology and different tissue distribution, cast doubt upon the functional equivalence of CD59 and either of the well‐characterized mouse Ly‐6 proteins.
Immunohistology of T cell differentiation in the thymus of H‐Y‐specific T cell receptor α/β transgenic mice
Authors: van Ewijk Willem , Kisielow Pawel , von Boehmer Harald 
Published: March 2007

AbstractWe examined the immunohistological aspects of the H‐Y specific T cell receptor (TcR) α/β transgene expression in the thymus of male and female transgenic (Tg) mice. Virtually all thymocytes expressed the β transgene in both the male and female thymus. Expression of accessory molecules (co‐receptors) in Tg mice deviated from control mice. In the male Tg thymus, CD8 expression was either low or absent on both cortical and medullary thymocytes. In contrast, in the thymus of female mice, CD8+ cells were found both in the cortex and in the medulla. The majority of medullary thymocytes was bright CD8+. This is in clear contrast to the CD8 distribution in control B6 mice, where only a few percent of medullary cells are CD8+. Similarily, the proportion of cells expressing CD4 antigens was reduced in the cortex and medulla of the thymus from male Tg mice, as compared to the thymus of female Tg mice and B6 control mice.Comparative analysis of the stromal cell types of the thymic microenvironments in the three groups of mice revealed that the cortical thymic microenvironment of male Tg mice differed, compared to that of female Tg mice. In particular, the deep cortex showed a closely packed meshwork of epithelial reticular cells. Moreover, H‐2Db molecules (which are the restricting elements for the Tg TcR α/β) were abnormally expressed in the thymic cortex of male mice. The cortical microenvironment in female mice, on the other hand, appeared normal.Together, the data indicate that TcR α/β transgene expression in male mice leads to an aberrant co‐receptor expression in both cortical and medullary lymphoid cells as well as an abnormal composition of the cortical microenvironment. Both phenomena may be the consequence of “negative selection” of developing H‐Y‐specific T cells, as it occurs only in the male Tg thymus. The absence of the H‐Y antigen, but presence of the restricting element H‐2Db in the thymic cortex of female mice, leads to accumulation of CD8+ in the medulla, a phenomenon interpreted as “positive selection”.
Reconstitution of H‐2 class I expression by gene transfection decreases susceptibility to natural killer cells of an EL4 class I loss variant
Authors: Sturmhöfel Knut , Hämmerling Günter J. 
Published: March 2007

AbstractSeveral reports have suggested that an inverse correlation exists between major histocompatibility complex class I expression and the susceptibility to natural killer (NK)‐mediatedlysis. For example, the increased class I expression induced by interferon‐γ was always accompanied by an increased resistance to NK lysis. Likewise, class I loss variants were often more NK susceptible than their normal counterparts.To investigate whether the inverse correlation between class I expression and NK susceptibility was fortuitous or whether the class I molecules were directly responsible for this effect we resorted to gene transfection studies. From the murine thymoma line EL4 an H‐2Db‐ and Kb‐negative variant S3 was selected. This variant was highly susceptible to NK lysis. S3 was found to have a defect in β2‐microglobulin gene expression. Therefore, restoration of Db and Kb expression could be achieved by transfection with the β2‐microglobulin gene. This resulted in a strong decrease in susceptibility to NK lysis to the level of the H‐2+ parental EL4. Transfection with class II genes had no effect. Blocking of the class I molecules on the H‐2+ cells with anti‐H‐2b F(ab')2 fragments increased the susceptibility to NK cells to the level of the H‐2− variant S3. These data demonstrate that the class I molecules on the targets are directly responsible for regulation of NK susceptibility but the mechanism is not clear. Possibly the class I molecules interfere with the unknown NK target structures.
Minor lymphocyte stimulating (Mls) gene products in mice influence their genetic resistance or susceptibility to induction of autoimmune encephalomyelitis
Authors: Ben‐Nun Avraham , Soffer David 
Published: March 2007

AbstractThe role of the major histocompatibility complex (MHC) gene products in the genetics of experimental autoimmune encephalomyelitis (EAE) is well established. Here we demonstrate how non‐MHC gene products, stimulatory to T cells specific to myelin basic protein (MBP), can affect the MHC control in determining genetic susceptibility or resistance to induction of EAE. I‐As‐restricted MBP‐specific T cells derived from SJL/J mice are shown to cross‐react with Mls‐2a gene products. The Mls‐2a gene product expressed by (SJL/J×BALB/c)F1 mice tolerize T cells recognizing I‐As/MBP and favor the development of I‐Es/d‐restricted MBP‐specific T cells mediating EAE in the (SJL/J×BALB/c)F1 mice. These I‐Es/d/MBP‐specific T cells, cross‐reactive with Mls‐1a, and the I‐As/MBP‐specific T cells, cross‐reactive with Mls‐2a gene products, are both eliminated by self tolerance mechanisms in the H‐2‐matched (SJL/J×DBA/2)F1 mice, expressing Mls‐1a2a gene products, and thereby confer genetic resistance to EAE on the (SJL/J×DBA/2)F1 mice bearing EAE‐permissive MHC alleles. These results reflect a developmental selection of a T cell repertoire to the self antigen MBP, imposed by self tolerance to self Mls gene products, which affect the genetic susceptibility to EAE. These studies also demonstrate that self tolerance to Mls gene products can strengthen the tolerance to organ‐specific self antigens such as MBP, which may not be expressed or which are absent in the thymus at the time of thymic selection.
Functional properties of CD19 B lymphocytes positively selected from buffy coats by immunomagnetic separation
Authors: Funderud Steinar , Erikstein Bjørn , Åsheim Hans Christian , Nustad Kjell , Stokke Trond , Blomhoff Heidi Kiil , Holte Harald , Smeland Erlend B. 
Published: March 2007

AbstractHere we report that human B lymphocytes can be positively selected directly from buffy coats applying the anti‐CD19 antibody AB1 coupled to magnetic beads. This isolation protocol is highly efficient and the isolated cell population is of very high purity and viability. As judged by cell cycle analysis and various parameters for cell activation, the cells are still in a resting state after isolation. Furthermore, different functional assays have shown that the isolation procedure does not interfere with either activation or proliferation/differentiation of CD 19 selected cells as compared to negatively isolated cells. As a consequence of cross‐linking during the isolation process, the CD 19 antigen is temporarily down‐regulated as measured by AB1 binding. Despite this decreased expression, monoclonal antibodies to the CD19 antigen nevertheless inhibited anti‐μ plus B cell growth factor induced B cell activation as reported also for negatively isolated cells. Taken together, the presented data strongly suggest that B cells isolated through the CD 19 antigen can be used in critical functional assays.
Distinct γ/δ T cell receptors define two subsets of circulating porcine CD2−CD4−CD8− T lymphocytes*
Authors: Hirt Werner , Saalmüller Armin , Reddehase Matthias J. 
Published: March 2007

AbstractThe species swine provides the only example for CD2+ and CD2− subsets of lg−CD4−CD8− lymphocytes with the propensity for homing to lymphoid tissue (Saalmüller et al., Eur. J. Immunol. 1989. 19: 2011). That the CD2−CD4−CD8− lymphocytes are bare of marker molecules that typify T lymphocytes raised the question of whether or not this cell type is descended from the T lymphocyte differentiation lineage. It is documented that expression of a phylogenetically conserved external epitope of T cell receptor γ/δ subdivides porcine CD2− lymphocytes into an epitope 86D+ minor and an 86D− major subset. Expression of distinct forms of the T cell receptor γ/δ, disulfide‐bonded N‐glycosylated surface heterodimers of under reducing conditions 38/40 and 37/40 kDa, respectively, hallmarks the CD2−86D+ and CD2−86D− subsets both as T lymphocytes.
Phenotype of intraepithelial lymphocytes in euthymic and athymic mice: Implications for differentiation of cells bearing a CD3‐associated γδ T cell receptor
Authors: de Geus Bernard , van den Enden Margit , Coolen Co , Nagelkerken Lex , van der Heijden Philip , Rozing Jan 
Published: March 2007

AbstractThis study was carried out to determine the exact phenotype of intraepithelial lymphocytes (IEL) in euthymic and athymic nude mice. The phenotype of IEL in euthymic and athymic mice is mainly CD3+CD8+. However, based on Thy‐1‐and CD3‐associated receptor expression we can subdivide the CD3CD8 population into different subpopulations in euthymic and athymic mice. In euthymic and athymic mice several CD3CD8 populations can be defined. One population expressing Thy‐1 and the T cell receptor (TcR) αβ is absent in athymic mice. Two other CD3+CD8+ populations can be detected in euthymic and athymic mice. Based on Northern blot and flow cytometric analysis we have to conclude that these populations express the CD3‐associated TcR γδ. One of the TcR γδ‐expressing populations also expresses Thy‐1 at low surface density. This is in contrast to the CD3CD8 population expressing the TcR αβ, which expresses Thy‐1 at high surface density. There are also, however, especially in athymic nude mice, significant numbers of CD3−CD8+ cells present with the same localization as IEL. The function of these cells is yet unknown. Using a probe for the δ chain we have shown that IEL preferentially express 2‐kb mRNA, while nearly no δ chain 1.7‐kb mRNA is expressed by these cells. This is in contrast to δ mRNA in thymocytes. Equal quantities of the 1.7‐ and 2.0‐kb δ chain mRNA species were found in RNA isolated from thymocytes.The results imply that CD3+CD8+ intestinal IEL expressing the CD3‐associated TcR γδ can differentiate in absence of the thymus and represent a thymusindependent lineage of cells bearing this receptor.
Low‐temperature inhibition of antigen processing and iron uptake from transferrin: Deficits in endosome functions at 18 °C
Authors: Harding Clifford V. , Unanue Emil R. 
Published: March 2007

AbstractAntigen processing involves endocytosis, proteolysis and denaturation of antigens to generate peptides that bind to major histocompatibility complex class II molecules (Ia) in a complex recognized by CD4+ T cells. Ia and antigen are internalized and processed intracellularly, but the exact subcellular site of antigen degradation and formation of the Ia‐peptide complex remains unclear. The present studies utilized low‐temperature incubation in an attempt to functionally block certain steps in the processing of the antigen hen egg white lysozyme (HEL) by peritoneal exudate cells (PEC) and TA3 B lymphoma cells. Ia endocytosis and uptake of HEL by PEC persisted at 18 °C, albeit at somewhat slower rates, but delivery of ligands to lysosomes was blocked. Under these conditions HEL catabolism and antigen processing were effectively blocked, although enough HEL was internalized at 18 °C to provide effective presentation during a subsequent incubation at 37 °C. In TA3 cells transferrin endocytosis and recycling were notably slowed at 18 °C, and iron uptake from transferrin by TA3 cells was completely blocked, indicating that certain specifically endosomal functions were inhibited at 18 °C. Thus, intracellular steps in antigen processing were blocked at 18 °C, corresponding to deficits in endosomal processing and targeting. These results demonstrate that antigen endocytosis and certain temperature‐sensitive endosomal and lysosomal processes are essential for antigen processing.
Structural characterization of human monoclonal cold agglutinins: Evidence for a distinct primary sequence‐defined VH4 idiotype
Authors: Silverman Gregg J. , Carson Dennis A. 
Published: March 2007

AbstractCold agglutinins that bind the developmentally regulated I red cell determinant occur naturally among human monoclonal IgM proteins. These autoantibodies are known to use light chains that derive mainly from the minor kappa III (xIII) variable region subgroup. The xIII subgroup is also highly expressed in monoclonal rheumatoid factors. However, while most monoclonal rheumatoid factors use structurally homologous heavy chains that derive from the VH1 family, information regarding the structure of the cold agglutinin heavy chains remains fragmentary. We demonstrate here that the xIII cold agglutinin autoantibodies exclusively use heavy chains that derive from the VH4 family. Furthermore, these autoantibody heavy chains all express the same primary sequence‐defined idiotype, corresponding to the second hypervariable region. These data indicate that cold agglutinins use a remarkably homogeneous subset of heavy chain variable regions. Moreover, unique patterns of preferential VH and VL pairing clearly distinguish the anti‐I cold agglutinins from all other known monoreactive autoantibodies.
The role of CD44, CD45, CD45RO, CD46 and CD55 as potential anti‐adhesion molecules involved in the binding of human tonsillar T cells to phorbol 12‐myristate 13‐acetate‐differentiated U‐937 cells
Authors: King Philip D. , Batchelor Adrian H. , Lawlor Patrick , Katz David R. 
Published: March 2007

AbstractIn this study, we have shown that human tonsillar T cells adhere to phorbol 12‐myristate 13‐acetate(PMA)‐differentiated U‐937 cells. To examine the molecular mechanisms involved, the effect of a panel of monoclonal antibodies upon this adhesion was assessed in a quantitative binding assay. Antibodies against LFA‐1 and ICAM‐1 inhibited binding, directly implicated these molecules in T cell‐PMA‐induced U‐937 adhesion. Furthermore, the adhesion was magnesium but not calcium dependent. Of the remaining antibodies that were tested, none of those against CD2, LFA‐3, Mac‐1, p150,95, CD43, CD45RA or CD56 affected binding. However, antibodies against CD44, CD45, CD45RO, CD46 and CD55 enhanced binding suggesting an anti‐adhesive role for these molecules during U‐937‐T cell interaction.
Macrophage‐secreted prostaglandin E2 potentiates immune complex‐induced B cell unresponsiveness
Authors: Stein Sidney H. , Phipps Richard P. 
Published: March 2007

AbstractImmune complexes (IC) are potent modulators of immune responses. In this report, we used an in vitro murine model system to investigate how two types of accessory cells pulsed with IC regulated B cell function. We demonstrate that IC‐pulsed macrophages (MΦ) induce hapten‐specific B cell unresponsiveness, whereas IC‐pulsed splenic lymphoid dendritic cells (LDC) and an LDC‐like tumor line caused an augmention of the antibody response. The mechanism by which IC‐pulsed MΦ diminished antibody production required two signals. The first was an antigen‐specific signal supplied by the IC, and the second a nonspecific co‐factor which was a product of MΦ cyclo‐oxygenase metabolism. Specifically, it was shown that prostaglandin E2 (PGE2) could function as this co‐factor. Interestingly, other prostanoids, such as PGF2α, did not function in this fashion. Purified fluorescein (FL+)‐specific B cells pulsed with IC exhibited a similar pattern of hapten‐specific unresponsiveness. Treatment of accessory cell‐free, FL+ B cells with PGE2 rendered them sensitive to subtolerogenic doses of soluble IC. Overall, our results suggest that one mechanism by which unresponsiveness can be induced involves both IC and PGE2, and that elevated levels of PGE2 sensitize B lymphocytes to antigen‐specific tolerogenic signals.
T cell receptor (TcR) β chain transgenic mice: Studies on allelic exclusion and on the TcR+ γ/δ population
Authors: Pircher Hanspeter , Ohashi Pamela , Miescher Guido , Lang Rosemarie , Zikopoulos Athanasios , Bürki Kurt , Mak Tak W. , Robson MacDonald H. , Hengartner Hans 
Published: March 2007

AbstractTo study allelic exclusion of TcR genes we analyzed two types (I and II) of TcR β transgenic mice. T cells derived from both types of mice contained similar amounts of transgenic RNA transcripts; however, surface expression of the transgenic β chain was drastically reduced in type II compared to type I. In type I transgenic mice, productive rearrangements and expression of endogenous TcR β genes were suppressed whereas on T cells of type II mice, both transgenic and endogenous TcR β chains were expressed on the surface of the same cell. These findings suggest that allelic exclusion of TcR genes in β transgenic mice depends on amount and/or onset of transgene expression during thymic development. Furthermore, TcR γ rearrangements and the population of TcR γ/δ‐bearing double‐negative CD4−CD8− thymocytes were reduced fivefold in type I transgenic animals. However, the Vγ usage and the γ/δ+ dendritic epidermal cell populations appeared normal. RNase protection analysis further revealed low levels of transgenic TcR β chain transcripts in TcR+ γ/δ CD4−CD8− thymocytes. These results suggest that the β transgene only quantitatively influences the γ/δ T cell compartment, and supports the independence of the γ/δ population.
Interleukin 7 is a growth factor for mature human T cells
Authors: Londei Marco , Verhoef Adrienne , Hawrylowicz Catherine , Groves Jill , de Berardinis Piergiuseppe , Feldmann Marc 
Published: March 2007

AbstractWe have studied the capacity of interleukin (IL) 7 to support the growth and expansion of human T cell clones of different phenotype and function. All the clones studied (CD4+CD8+, CD4−CD8− T cell receptor α/β or γ/δ) responded to IL 7. The proliferative response of all the T cell clones induced by IL 7 was routinely less than to IL 2, but comparable to the IL 4 response. IL 7 also induced the proliferation of resting, freshly prepared peripheral blood mononuclear cells (PBMC) or T cell‐enriched (E+) cells. The pattern of proliferation observed in the presence of IL 7 was similar, but lower in magnitude, to that induced by IL 2. In both these cells populations the response to lymphokines alone was always less than the response to lymphokines plus insolubilized anti‐CD3 monoclonal antibody. In contrast IL 4 produced a different pattern of responsiveness, as significant proliferation was observed only on PBMC costimulated with anti‐CD3. The possibility that IL 7 mediates its growth stimulation by the IL 2 pathway was excluded by the incapacity of anti‐IL 2 or anti‐Tac monoclonal antibody, in concentrations which blocked IL 2‐dependent proliferation, to inhibit IL 7‐dependent growth. We conclude that IL 7 is a major growth factor for human mature T cells, and its activity is not limited to lymphocyte progenitors.
Regulation of Ig gene expression in normal lymphocytes. I. The half‐life of secreted μ chain mRNA differs from that of membrane μ chain mRNA in resting and activated B cells
Authors: Berberich Ingolf , Schimpl Anneliese 
Published: March 2007

AbstractResting and activated B lymphocytes were used to study the stability of μ‐specific precursor and mature mRNA. Resting cells which predominantly process the μ precursor towards μm do so rather slowly as reflected in a precursor half‐life (T1/2) of 1‐2 h. The small amount of secreted μ chain mRNA is fairly stable (T1/2 ≈ 8 h) compared to membrane μ chain (T1/2 ≈ 4 h). After activation the precursor processing is very fast (T1/2 ≈ 10 min) and the stability of μ2, which now predominates, increases (T1/2 ≈ 16 h) while the half‐life of μm remains at about 4 h. The data indicate that normal B cells regulate μ‐specific mRNA stability differently from tumor cells of the B cell lineage.
Structural nature of the interaction between T lymphocyte surface molecule CD4 and the intracellular protein tyrosine kinase Ick
Authors: Vega Miguel A. , Kuo Mei‐Chang , Carrera Ana C. , Strominger Jack L. 
Published: March 2007

AbstractThe strong non‐covalent interactions between T lymphocyte surface CD4 or CD8 molecules and the intracellular membrane‐associated protein tyrosine kinase Ick are likely to mediate the role of CD4 and CD8 molecules in the immune response. The delineation of the structural nature of the CD4/Ick and CD8/Ick complexes is important for the understanding of the biochemical and functional significance of the interactions. Complementary charged regions in the C‐terminal intracyto‐plasmic portions of CD4 or CD8, and in the N‐terminal region of protein tyrosine kinase Ick were noted. Peptides spanning these regions, residues 417 to 429 of CD4 and 10 to 22 of Ick, were found to specifically dissociate these two molecules in CD4/Ick complexes. A structural model of the interaction that accounts for its high stability is proposed.