scholarly journals LB712 Transcriptomic profiling of Necrobiotic Xanthogranuloma and Necrobiosis Lipoidica provides insight into pathogenic role of T and B cells

2021 ◽  
Vol 141 (9) ◽  
pp. B2
Author(s):  
W. Liakos ◽  
A. Toussi ◽  
A. Merleev ◽  
A. Marusina ◽  
A. Riera Leal ◽  
...  
Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2823-2823
Author(s):  
Sue E. Blackwell ◽  
Bernd Jahrsdoerfer ◽  
James E. Wooldridge ◽  
Jian Huang ◽  
Melinda W. Andreski ◽  
...  

Abstract Interleukin 21 (IL-21), a recently discovered cytokine with structural homology to IL-2, IL-4 and IL-15, has pleiotropic effects on lymphocyte populations including NK, T and B cells and is currently undergoing early clinical evaluation. We explored the effect of the combination of IL-21 and immunostimulatory CpG ODN on B chronic lymphocytic leukemia (B-CLL), and other CD5-positive B cells. IL-21 plus CpG ODN were synergistic in their ability to induce apoptosis of the B-CLL cells, and also induced production and secretion of granzyme B from the B-CLL cells. B-CLL cells treated with IL-21 and CpG ODN were capable of inducing apoptosis of untreated autologous B-CLL cells. This bystander killing was inhibited by anti-granzyme B antibodies. The effect was observed in all cases of CD5-positive B-CLL, but not in CD5-negative B-CLL samples. IL-21 plus CpG ODN also induced granzyme B production and apoptosis of benign CD5-positive B1 cells obtained from umbilical cord blood. In contrast, the number of CD5-negative B2 cells increased in the same samples during in vitro culture, resulting in a decreased ratio of CD5-positive to CD5-negative cord blood B cells (Fig. 1). Our results indicate the combination of IL-21 and CpG ODN is able to induce apoptosis of both benign and malignant CD5-positive B cells. Given the suspected role of B1 cells in autoimmune diseases, our findings could have important implications for the understanding of their pathogenetic mechanisms. These results might also open new avenues for the development of novel therapies for both autoimmune dieseases and CD5-positive B-CLL. Figure 1. IL- 21 and CpG ODN therapy selectively eliminates CD5 positive B cells in cord blood. Figure 1. IL- 21 and CpG ODN therapy selectively eliminates CD5 positive B cells in cord blood.


2005 ◽  
Vol 99 (2) ◽  
pp. 198-208 ◽  
Author(s):  
Dorothea Stahl ◽  
Sébastien Lacroix-Desmazes ◽  
Namita Misra ◽  
Marina Karmochkine ◽  
Srini V. Kaveri ◽  
...  

2021 ◽  
Author(s):  
Krista L Newell ◽  
Mitchell J Waldran ◽  
Stephen J Thomas ◽  
Timothy P Endy ◽  
Adam Tully Waickman

Conventional methods for quantifying and phenotyping antigen-specific lymphocytes can rapidly deplete irreplaceable specimens. This is due to the fact that antigen-specific T and B cells have historically been analyzed in independent assays each requiring millions of cells. A technique that facilitates the simultaneous detection of antigen-specific T and B cells would allow for more thorough immune profiling with significantly reduced sample requirements. To this end, we developed the B And T cell Tandem Lymphocyte Evaluation (BATTLE) assay, which allows for the simultaneous identification of SARS-CoV-2 Spike reactive T and B cells using an optimized Activation Induced Marker (AIM) T cell assay and dual-color B cell antigen probes. Using this assay, we demonstrate that antigen-specific B and T cell subsets can be identified simultaneously using conventional flow cytometry platforms and provide insight into the differential effects of mRNA vaccination on B and T cell populations following natural SARS-CoV-2 infection.


Author(s):  
Fabio Sallustio ◽  
Claudia Curci ◽  
Nada Chaoul ◽  
Giulia Fontò ◽  
Gabriella Lauriero ◽  
...  

Abstract Background Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulonephritis. The role of the microbiota and mucosal immunity in the pathogenesis of IgAN remains a key element. To date, the hypothetical relationship between commensal bacteria, elevated tumour necrosis factor (TNF) superfamily member 13 [also known as B-cell activating factor (BAFF)] levels, perturbed homoeostasis of intestinal-activated B cells and intestinal IgA class switch has not been clearly shown in IgAN patients. Methods We studied the intestinal–renal axis connections, analysing levels of BAFF, TNF ligand superfamily member 13 (APRIL) and intestinal-activated B cells in IgAN patients, healthy subjects (HSs) and patients with non-IgA glomerulonephritides. Results IgAN patients had increased serum levels of BAFF cytokine, correlating with higher amounts of five specific microbiota metabolites, and high APRIL cytokine serum levels. We also found that subjects with IgAN have a higher level of circulating gut-homing (CCR9+ β7 integrin+) regultory B cells, memory B cells and IgA+ memory B cells compared with HSs. Finally, we found that IgAN patients had high levels of both total plasmablasts (PBs) and intestinal-homing PBs. Interestingly, PBs significantly increased in IgAN but not in patients with other glomerulonephritides. Conclusions Our results demonstrate a significant difference in the amount of intestinal-activated B lymphocytes between IgAN patients and HSs, confirming the hypothesis of the pathogenic role of intestinal mucosal hyperresponsiveness in IgAN. The intestinal–renal axis plays a crucial role in IgAN and several factors may contribute to its complex pathogenesis and provide an important area of research for novel targeted therapies to modulate progression of the disease.


2019 ◽  
Vol 6 (4) ◽  
pp. e563
Author(s):  
Rehana Z. Hussain ◽  
Petra D. Cravens ◽  
William A. Miller-Little ◽  
Richard Doelger ◽  
Valerie Granados ◽  
...  

ObjectiveThe goal of this study was to investigate the role of CD 19+ B cells within the brain and spinal cord during CNS autoimmunity in a peptide-induced, primarily T-cell–mediated experimental autoimmune encephalomyelitis (EAE) model of MS. We hypothesized that CD19+ B cells outside the CNS drive inflammation in EAE.MethodsWe generated CD19.Cre+/− α4-integrinfl/fl mice. EAE was induced by active immunization with myelin oligodendrocyte glycoprotein peptide (MOGp35-55). Multiparameter flow cytometry was used to phenotype leukocyte subsets in primary and secondary lymphoid organs and the CNS. Serum cytokine levels and Ig levels were assessed by bead array. B-cell adoptive transfer was used to determine the compartment-specific pathogenic role of antigen-specific and non–antigen-specific B cells.ResultsA genetic ablation of α4-integrin in CD19+/− B cells significantly reduced the number of CD19+ B cells in the CNS but does not affect EAE disease activity in active MOGp35-55-induced disease. The composition of B-cell subsets in the brain, primary lymphoid organs, and secondary lymphoid organs of CD19.Cre+/− α4-integrinfl/fl mice was unchanged during MOGp35-55-induced EAE. Adoptive transfer of purified CD19+ B cells from CD19.Cre+/− α4-integrinfl/fl mice or C57BL/6 wild-type (WT) control mice immunized with recombinant rMOG1-125 or ovalbumin323-339 into MOGp35-55-immunized CD19.Cre+/− α4-integrinfl/fl mice caused worse clinical EAE than was observed in MOGp35-55-immunized C57BL/6 WT control mice that did not receive adoptively transferred CD19+ B cells.ConclusionsObservations made in CD19.Cre+/− α4-integrinfl/fl mice in active MOGp35-55-induced EAE suggest a compartment-specific pathogenic role of CD19+ B cells mostly outside of the CNS that is not necessarily antigen specific.


Vaccine ◽  
2019 ◽  
Vol 37 (34) ◽  
pp. 4787-4793 ◽  
Author(s):  
Sachin Mani ◽  
Franklin R. Toapanta ◽  
Monica A. McArthur ◽  
Firdausi Qadri ◽  
Ann-Mari Svennerholm ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiugang Zhu ◽  
Ke Rui ◽  
Shengjun Wang ◽  
Jie Tian

With the ability to induce T cell activation and elicit humoral responses, B cells are generally considered as effectors of the immune system. However, the emergence of regulatory B cells (Bregs) has given new insight into the role of B cells in immune responses. Bregs exhibit immunosuppressive functions via diverse mechanisms, including the secretion of anti-inflammatory cytokines and direct cell contact. The balance between Bregs and effector B cells is important for the immune tolerance. In this review, we focus on recent advances in the characteristics of Bregs and their functional roles in autoimmunity.


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