Saijai Cheunsuk, Tom Hsu, M Eric Gershwin, Christopher L Bowlus
{"title":"Analysis of the IDDM candidate gene Prss16 in NOD and NON mice.","authors":"Saijai Cheunsuk, Tom Hsu, M Eric Gershwin, Christopher L Bowlus","doi":"10.1080/10446670310001593497","DOIUrl":"https://doi.org/10.1080/10446670310001593497","url":null,"abstract":"<p><p>The thymus-specific serine protease Prss16 is highly expressed by the epithelial cells in the thymic cortex. It has been suggested to play an important role in the positive selection of T cells through the antigen presention pathway of the cortical antigen presenting cells. Recently, the gene encoding Prss16 has been linked to insulin dependent diabetes mellitus (IDDM) susceptibility independent of HLA-DR3 suggesting the Prss16 may be involved in the development of autoimmune disease. Due to the similarities of the gene structure and expression pattern between the human and mouse genes, we compared Prss16 between non-obese diabetic (NOD) and non-obese non-diabetic (NON) mice. Analysis of the Prss16 coding region failed to identify any differences in sequence. Northern analysis and semi-quantitative reverse transcriptase polymerase chain reaction showed that the mRNA was equal in size and abundance in the two strains. In situ hybridization showed similar patterns of staining. Therefore, our data suggests that there is no significant different in the gene structure, transcription level, and expression pattern of Prss16 gene between NOD and NON mice.</p>","PeriodicalId":77106,"journal":{"name":"Developmental immunology","volume":"9 4","pages":"183-6"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10446670310001593497","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24519615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bernadette Nabarra, Catherine Martinon, Cécile Godard, Florence Vasseur, Geoffroy de Ribains, Lucile Miquerol, Axel Kahn, Sophie Ezine
{"title":"Early steps of a thymic tumor in SV40 transgenic mice: hyperplasia of medullary epithelial cells and increased mature thymocyte numbers disturb thymic export.","authors":"Bernadette Nabarra, Catherine Martinon, Cécile Godard, Florence Vasseur, Geoffroy de Ribains, Lucile Miquerol, Axel Kahn, Sophie Ezine","doi":"10.1080/10446670310001593532","DOIUrl":"https://doi.org/10.1080/10446670310001593532","url":null,"abstract":"<p><p>Bone marrow progenitors migrate to the thymus, where they proliferate and differentiate into immunologically competent T cells. In this report we show that mice transgenic for SV40 T and t antigens under the control of the L-pyruvate kinase promoter develop, in a first step, thymic hyperplasia of both thymocytes and epithelial cells. Morphological studies (histology, immunohistolabeling and electron microscopy) revealed modifications of the thymic microenvironment and gradual expansion of medullary epithelial cells in 1 month-old mice, taking over the cortical region. Then, a thymic carcinoma develops. Two-color labeling of frozen sections identified the transgene in medullary epithelial cells. Flow cytometry analysis demonstrated a marked increase in mature CD4+ and CD8+ thymocytes in adult mice (39 +/- 10 x 10(6) in transgenic mice and 12 +/- 5 x 10(6) in age-matched controls). Furthermore, thymocyte export was disturbed.</p>","PeriodicalId":77106,"journal":{"name":"Developmental immunology","volume":"9 4","pages":"223-31"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10446670310001593532","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24520112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deborah K Dunn-Walters, Alex Belelovsky, Hanna Edelman, Monica Banerjee, Ramit Mehr
{"title":"The dynamics of germinal centre selection as measured by graph-theoretical analysis of mutational lineage trees.","authors":"Deborah K Dunn-Walters, Alex Belelovsky, Hanna Edelman, Monica Banerjee, Ramit Mehr","doi":"10.1080/10446670310001593541","DOIUrl":"https://doi.org/10.1080/10446670310001593541","url":null,"abstract":"<p><p>We have developed a rigorous graph-theoretical algorithm for quantifying the shape properties of mutational lineage trees. We show that information about the dynamics of hypermutation and antigen-driven clonal selection during the humoral immune response is contained in the shape of mutational lineage trees deduced from the responding clones. Age and tissue related differences in the selection process can be studied using this method. Thus, tree shape analysis can be used as a means of elucidating humoral immune response dynamics in various situations.</p>","PeriodicalId":77106,"journal":{"name":"Developmental immunology","volume":"9 4","pages":"233-43"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10446670310001593541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24520113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer C C Neale, Judith A van de Water, James T Harvey, Ronald S Tjeerdema, M Eric Gershwin
{"title":"Proliferative responses of harbor seal (Phoca vitulina) T lymphocytes to model marine pollutants.","authors":"Jennifer C C Neale, Judith A van de Water, James T Harvey, Ronald S Tjeerdema, M Eric Gershwin","doi":"10.1080/10446670310001593523","DOIUrl":"https://doi.org/10.1080/10446670310001593523","url":null,"abstract":"<p><p>In recent years, population declines related to viral outbreaks in marine mammals have been associated with polluted coastal waters and high tissue concentrations of certain persistent, lipophilic contaminants. Such observations suggest a contributing role of contaminant-induced suppression of cell-mediated immunity leading to decreased host resistance. Here, we assessed the effects of the prototypic polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (B[a]P), and two polychlorinated biphenyls (PCBs), CB-156 and CB-80, on the T-cell proliferative response to mitogen in harbor seal peripheral lymphocytes. Despite the variability associated with our samples from free-ranging harbor seals, we observed a clear suppressive effect of B[a]P (10 uM) exposure on T cell mitogenesis. Exposures to 10 uM CB-156 and CB-80, and 1.0 and 0.1 uM B[a]P, did not produce significant depression in lymphoproliferation. Exposure to the model PAH at 10 uM resulted in a 61% (range 34-97%) average reduction in lymphoproliferation. We were able to rule out a direct cytotoxic effect of B[a]P, indicating that observed effects were due to altered T cell function. Based on our in vitro results, we hypothesize that extensive accumulation of PAH by top-trophic-level marine mammals could alter T cell activation in vivo and impaired cell-mediated immunity against viral pathogens.</p>","PeriodicalId":77106,"journal":{"name":"Developmental immunology","volume":"9 4","pages":"215-21"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10446670310001593523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24520111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
France Mélot, Caroline Thielen, Thouraya Labiet, Sabine Eisher, Olivier Jolois, Ernst Heinen, Nadine Antoine
{"title":"Do bovine lymphocytes express a peculiar prion protein?","authors":"France Mélot, Caroline Thielen, Thouraya Labiet, Sabine Eisher, Olivier Jolois, Ernst Heinen, Nadine Antoine","doi":"10.1080/10446670310001593550","DOIUrl":"https://doi.org/10.1080/10446670310001593550","url":null,"abstract":"<p><p>The cellular prion protein (PrPc) is a glycolipid-anchored cell surface protein that usually exhibits three glycosylation states. Its post-translationally modified isoform, PrPsc, is involved in the pathogenesis of various transmissible spongiform encephalopathies (TSEs). In bovine species, BSE infectivity appears to be restricted to the central nervous system; few or no detectable infectivity is found in lymphoid tissues in contrast to scrapie or variant CJD. Since expression of PrPc is a prerequisite for prion replication, we have investigated PrPc expression by bovine immune cells. Lymphocytes from blood and five different lymph organs were isolated from the same animal to assess intra- and interindividual variability of PrPc expression, considering six individuals. As shown by flow cytometry, this expression is absent or weak on granulocytes but is measurable on monocytes, B and T cells from blood and lymph organs. The activation of the bovine cells produces an upregulation of PrPc. The results of our in vitro study of PrPc biosynthesis are consistent with previous studies in other species. Interestingly, western blotting experiments showed only one form of the protein, the diglycosylated band. We propose that the glycosylation state could explain the lack of infectivity of the bovine immune cells.</p>","PeriodicalId":77106,"journal":{"name":"Developmental immunology","volume":"9 4","pages":"245-52"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10446670310001593550","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24520114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Friedrich Haag, Dunja Freese, Felix Scheublein, Wiebke Ohlrogge, Sahil Adriouch, Michel Seman, Friedrich Koch-Nolte
{"title":"T cells of different developmental stages differ in sensitivity to apoptosis induced by extracellular NAD.","authors":"Friedrich Haag, Dunja Freese, Felix Scheublein, Wiebke Ohlrogge, Sahil Adriouch, Michel Seman, Friedrich Koch-Nolte","doi":"10.1080/10446670310001593514","DOIUrl":"https://doi.org/10.1080/10446670310001593514","url":null,"abstract":"<p><p>Extracellular nucleotides such as ATP and NAD can profoundly affect the functions of lymphocytes, macrophages, and other cells. We have recently shown that extracellular NAD induces rapid apoptosis in naive T cells by a mechanism involving the ADP-ribosylation of cell surface molecules. In the present paper, we describe that T cells of different developmental stages differ in their sensitivity to NAD-induced apoptosis. Thymocytes were less susceptible than peripheral lymph node T cells, and freshly activated cells were more resistant than resting cells. Sensitivity to NAD-induced apoptosis generally correlated with expression of the ADP-ribosyltransferase ART2.2, which is not expressed on thymocytes and shed from peripheral T cells upon activation. Our findings suggest that NAD-induced apoptosis does not play a role during thymic selection of T cells, but rather may play a role by preventing the activation of unwanted bystander T cells during an immune response, and thus may participate in the control of autoimmunity.</p>","PeriodicalId":77106,"journal":{"name":"Developmental immunology","volume":"9 4","pages":"197-202"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10446670310001593514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24520109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter M Dammers, Monique E Lodewijk, André Zandvoort, Frans G M Kroese
{"title":"Marginal zone B cells in neonatal rats express intermediate levels of CD90 (Thy-1).","authors":"Peter M Dammers, Monique E Lodewijk, André Zandvoort, Frans G M Kroese","doi":"10.1080/10446670310001593488","DOIUrl":"https://doi.org/10.1080/10446670310001593488","url":null,"abstract":"<p><p>Here we show that marginal zone (MZ)-B cells in rats can already be detected in neonatal spleen from two days after birth. At this time point, morphologically distinct MZs are not present yet and the vast majority of B cells in spleen are located in a concentric area surrounding the T cell zones (PALS). Before MZs are obviously detectable in spleen (14 days after birth), MZ-B cells seem to be enriched at the outer zones of the concentric B cell areas. Similar to adult rats, neonatal MZ-B cells are intermediate-sized cells that express high levels of surface (s)IgM and HIS57 antigen, and low levels of sIgD and CD45R (HIS24). We show here, however, that in contrast to adult MZ-B cells, MZ-B cells (and also recirculating follicular (RF)-B cells) in neonatal rats express higher levels of CD90 (Thy-1). In adult rats, expression of CD90 on the B cell lineage is confined to immature B cells. We speculate that the expression of CD90 on neonatal MZ-B cells may have implications for their responsiveness to polysaccharide (T cell-independent type 2) antigens.</p>","PeriodicalId":77106,"journal":{"name":"Developmental immunology","volume":"9 4","pages":"187-95"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10446670310001593488","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24520108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Conclusions from two model concepts on germinal center dynamics and morphology.","authors":"Michael Meyer-Hermann, Tilo Beyer","doi":"10.1080/1044-6670310001597060","DOIUrl":"https://doi.org/10.1080/1044-6670310001597060","url":null,"abstract":"<p><p>Germinal centers (GC) are an essential part of the humoral immune response. They develop a clear structure during maturation: Centroblasts and centrocytes are separated into two zones, the dark and the light zone. The mechanisms leading to this specific morphology as well as the reason for zone-depletion during a later phase of the GC reaction have not clearly been revealed in experiment. We discuss and weigh possible mechanisms of dark and light zone development in the framework of two mathematical models. In a comparative approach we formulate constraints on typical lymphocyte velocities in GCs which are characteristic for the different proposed mechanisms.</p>","PeriodicalId":77106,"journal":{"name":"Developmental immunology","volume":"9 4","pages":"203-14"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1044-6670310001597060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24520110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exposure to environmental antigens induces the development of germinal centers in premature neonates.","authors":"N Wittenbrink, M Zemlin, K Bauer, C Berek","doi":"10.1080/1044667031000137665","DOIUrl":"https://doi.org/10.1080/1044667031000137665","url":null,"abstract":"<p><p>The immune response of the neonate is poor and is dependent on passive immunity provided by maternal Ig. However, here we show that exposure of the neonate to environmental antigens induces a germinal center (GC) reaction. In the peripheral blood of premature infants one finds IgG class switched B cells expressing a selected V-gene repertoire. These data suggest that restrictions in the repertoire rather than immaturity of the immune system is responsible for the poor immune responses of the neonate.</p>","PeriodicalId":77106,"journal":{"name":"Developmental immunology","volume":"9 3","pages":"177-9"},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1044667031000137665","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22502092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carl de Trez, Annette van Acker, Georgette Vansanten, Jacques Urbain, Maryse Brait
{"title":"Altered affinity maturation in primary response to (4-hydroxy-3-nitrophenyl) acetyl (NP) after autologous reconstitution of irradiated C57BL/6 mice.","authors":"Carl de Trez, Annette van Acker, Georgette Vansanten, Jacques Urbain, Maryse Brait","doi":"10.1080/1044667031000137593","DOIUrl":"https://doi.org/10.1080/1044667031000137593","url":null,"abstract":"<p><p>Immune responses developing in irradiated environment are profoundly altered. The memory anti-arsonate response of A/J mice is dominated by a major clonotype encoded by a single gene segment combination called CRIA. In irradiated and autoreconstituted A/J mice, the level of anti-ARS antibodies upon secondary immunization is normal but devoid of CRIA antibodies. The affinity maturation process and the somatic mutation frequency are reduced. Isotype switching and development of germinal centers (GC) are delayed. The primary antibody response of C57BL/6 mice to the hapten (4-hydroxy-3-nitrophenyl) acetyl (NP)-Keyhole Limpet Hemocyanin (KLH) is dominated by antibodies encoded by a family of closely related VH genes associated with the expression of the lambda1 light chain.We investigated the anti-NP primary response in irradiated and autoreconstituted C57BL/6 mice. We observed some splenic alterations as previously described in the irradiated A/J model. Germinal center reaction is delayed although the extrafollicular foci appearance is unchanged. Irradiated C57BL/6 mice are able to mount a primary anti-NP response dominated by lambda1 positive antibodies but fail to produce high affinity NP-binding IgG1 antibodies. Following a second antigenic challenge, irradiated mice develop enlarged GC and foci. Furthermore, higher affinity NP-binding IgG1 antibodies are detected.</p>","PeriodicalId":77106,"journal":{"name":"Developmental immunology","volume":"9 3","pages":"119-25"},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1044667031000137593","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22502792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}