scholarly journals Subclass restriction of murine antibodies. II. The IgG plaque-forming cell response to thymus-independent type 1 and type 2 antigens in normal mice and mice expressing an X-linked immunodeficiency.

1980 ◽  
Vol 151 (4) ◽  
pp. 853-862 ◽  
Author(s):  
J Slack ◽  
G P Der-Balian ◽  
M Nahm ◽  
J M Davie

Antigens have been classified previously into three categories, thymus-dependent (TD), thymus-independent type (TI) 1, and TI-2, based upon thymic dependence and ability to stimulate an immunodeficient strain of mouse, CBA/N. Here we demonstrate that the different antigen classes elicit IgG antibodies of different subclasses. TD antigens stimulate predominantly IgG1 antibodies, with smaller amounts of IgG2 and IgG3 being expressed. TI-1 antigens stimulate almost no IgG1 antibodies and equal amounts of IgG2 and IgG3. TI-2 antigens elicit predominantly IgG3 antibodies. Mice expressing the CBA/N phenotype are known to be nonresponsive to TI-2 antigens. This was confirmed in this study. In addition, we demonstrate that the IgG3 component of the response to TI-1 antigens is virtually absent in mice expressing the CBA/N phenotype, which supports our previous finding that the CBA/N defect may be restricted to a B-lymphocyte subpopulation containing most of the precursors of IgG3-secreting cells.

Luminescence ◽  
2014 ◽  
Vol 30 (5) ◽  
pp. 649-654 ◽  
Author(s):  
Qian‐Ni Liang ◽  
Jian‐Wei Zhou ◽  
Tian‐Cai Liu ◽  
Guan‐Feng Lin ◽  
Zhi‐Ning Dong ◽  
...  

2018 ◽  
Author(s):  
Rajesh Ponnusamy ◽  
Ritika Khatri ◽  
Paulo B. Correia ◽  
Erika Mancini ◽  
Paul J. Farrell ◽  
...  

AbstractNatural variation separates Epstein-Barr virus (EBV) into type 1 and type 2 strains. Type 2 EBV is less transformingin vitrodue to sequence differences in the EBV transcription factor EBNA2. This correlates with reduced activation of the EBV oncogene LMP1 and some cell genes. Transcriptional activation by type 1 EBNA2 can be suppressed through the binding of two PXLXP motifs in its transactivation domain (TAD) to the dimeric coiled-coil MYND domain (CC-MYND) of the BS69 repressor protein (ZMYND11). We identified a third conserved PXLXP motif in type 2 EBNA2. We found that type 2 EBNA2 peptides containing this motif bound BS69CC-MYNDefficiently and that the type 2 EBNA2TADbound an additional BS69CC-MYNDmolecule. Full-length type 2 EBNA2 also bound BS69 more efficiently in pull-down assays. Molecular weight analysis and low-resolution structures obtained using small-angle X-ray scattering showed that three BS69CC-MYNDdimers bound two molecules of type 2 EBNA2TAD, in line with the dimeric state of full-length EBNA2in vivo. Importantly, mutation of the third BS69 binding motif in type 2 EBNA2 improved B-cell growth maintenance. Our data indicate that increased association with BS69 restricts growth promotion by EBNA2 and may contribute to reduced B-cell transformation by type 2 EBV.Author summaryEpstein-Barr virus (EBV) drives the development of many human cancers worldwide including specific types of lymphoma and carcinoma. EBV infects B lymphocytes and immortalises them, thus contributing to lymphoma development. The virus promotes B lymphocyte growth and survival by altering the level at which hundreds of genes are expressed. The EBV protein EBNA2 is known to activate many growth-promoting genes. Natural variation in the sequence of EBNA2 defines the two main EBV strains: type 1 and type 2. Type 2 strains immortalise B lymphocytes less efficiency and activate some growth genes poorly, although the mechanism of this difference is unclear. We now show that sequence variation in type 2 EBNA2 creates a third site of interaction for the repressor protein (BS69, ZMYND11). We have characterised the complex formed between type 2 EBNA2 and BS69 and show that three dimers of BS69 form a bridged complex with two molecules of type 2 EBNA2. We demonstrate that mutation of the additional BS69 interaction site in type 2 EBNA2 improves its growth-promoting function. Our results therefore provide a molecular explanation for the different B lymphocyte growth promoting activities of type 1 and type 2 EBV. This aids our understanding of immortalisation by EBV.


Author(s):  
I. Dardick ◽  
T. Bladon ◽  
N. Sinnott ◽  
A. Dardick ◽  
R. Hall ◽  
...  

Despite the important -role of nuclear morphology in tissue recognition and tumor diagnosis, the variation of this organelle in terms of size, shape and condensed chromatin organization, and the mechanisms involved, are poorly understood. Since antigenic and mitogenic activation of the normal lymphocyte leads to considerable alteration in the nucleus in terms of size and condensed chromatin distribution, this cell type affords an opportunity to study this phenomenon in detail. Previous studies have shown that a sizeable amount of nuclear protein is made during lymphocyte transformation.This ultrastructural morphometric image analysis was undertaken in an attempt to quantitate modifications in nuclear components during T-lymphocyte (human peripheral) and B-lymphocyte (mouse spleen) transformation induced with concanavalin A (Con A) and bacterial lipopolysaccharide (LPS) respectively. Cell suspensions and tissue samples were obtained at varying intervals after mitogen stimulation. Random nuclei, both unstimulated (Type 1), partially transformed (Type 2), and fully transformed (Type 3) were photographed (Figs 1 to 3).


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Alessandro P. Delitala ◽  
Giovanni M. Pes ◽  
Hoda M. Malaty ◽  
Gavino Pisanu ◽  
Giuseppe Delitala ◽  
...  

Background.Type 1 diabetes (T1D) and type 2 diabetes (T2D) have been linked toHelicobacter pyloriinfection, although results are conflicting. No previous study addressed a possible link betweenH. pyloriinfection and latent autoimmune diabetes in adults (LADA). In this study, a correlation amongH. pyloriinfection and the risk of autoimmune diabetes in comparison with T2D was investigated.Methods.Sera from 234 LADA patients, 105 patients with late-onset T1D, and 156 patients with T2D were analyzed for anti-H. pyloriand the cytotoxin-associated antigen (CagA) IgG antibodies. Results. H. pyloriseroprevalence was comparable in LADA (52%), late-onset T1D (45%), and T2D (49%) with no gender differences. The seroprevalence of CagA IgG was significantly higher in autoimmune diabetes (late-onset T1D: 45%, LADA: 40%) compared to T2D (25%;p<0.028).Conclusions.AlthoughH. pyloriseroprevalence was similar in LADA, T1D, and T2D, anti-CagA positivity was significantly increased among patients with autoimmune diabetes, suggesting that more virulentH. pyloristrains might be a trigger for immune mechanisms involved in their pathogenesis.


2021 ◽  
Vol 23 (4) ◽  
pp. 903-908
Author(s):  
Yu. V. Zhukova ◽  
A. A. Alshevskaya ◽  
F. D. Kireev ◽  
O. A. Chumasova ◽  
N. S. Shkaruba ◽  
...  

A pleiotropic cytokine TNFα is an important inflammatory mediator of a number of diseases; its biological functions are fulfilled through two different receptors, TNFR1 and TNFR2. Changes in the ratio between these types of receptors shifting the balance between the pro-apoptotic and proliferation signaling pathways play a crucial role in eliciting the cell response to TNFα. The pathological processes in the body can alter the levels of TNFR1 and TNFR2 expression on the cells involved in disease development. Therefore, this study was aimed at investigating the level of co-expression of type 1 and 2 TNFα receptors in the major subpopulations of peripheral blood cells in patients with rheumatoid arthritis (RA) and bronchial asthma (BA). The greatest changes in the percentage of cells expressing TNFR1 and TNFR2 were revealed for the B-lymphocyte subpopulation. For the T-lymphocyte subpopulation, there were some differences in the percentage of cells expressing exclusively TNFR1 in RA and BA patients compared with those in healthy subjects, as well as between the RA and BA groups. A higher percentage of double-negative monocytes was observed in patients with BA and RA compared to healthy subjects. These findings indicate that the coexpression profile of TNFR1 and TNFR2 receptors in patients with RA and BA differ within these groups as well as compared to that in healthy subjects. These immune cell populations are actively involved in the pathogenesis of both rheumatoid arthritis and bronchial asthma, so the results may indicate that these cells might show different responses to TNFα as the percentage and the number of receptors on their surface vary. 


2008 ◽  
Vol 38 (15) ◽  
pp. 18
Author(s):  
SHERRY BOSCHERT
Keyword(s):  

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