scholarly journals Immune Tolerance Negatively Regulates B Cells in Knock-In Mice Expressing Broadly Neutralizing HIV Antibody 4E10

2013 ◽  
Vol 191 (6) ◽  
pp. 3186-3191 ◽  
Author(s):  
Colleen Doyle-Cooper ◽  
Krystalyn E. Hudson ◽  
Anthony B. Cooper ◽  
Takayuki Ota ◽  
Patrick Skog ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Tolerance ◽  
Antibody 4E10

scholarly journals TLR9-Deficiency in B Cells Promotes Immune Tolerance via IL-10 in a Type 1 Diabetes Mouse Model

Diabetes ◽  
2020 ◽  
pp. db200373
Author(s):  
Sha Sha ◽  
James A Pearson ◽  
Jian Peng ◽  
Youjia Hu ◽  
Juan Huang ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
B Cells ◽  
Mouse Model ◽  
Immune Tolerance ◽  
Diabetes Mouse

Role of Der p 1–specific B cells in immune tolerance during 2 years of house dust mite–specific immunotherapy

2019 ◽  
Vol 143 (3) ◽  
pp. 1077-1086.e10 ◽  
Author(s):  
Tadech Boonpiyathad ◽  
Willem van de Veen ◽  
Oliver Wirz ◽  
Milena Sokolowska ◽  
Beate Rückert ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Tolerance ◽  
House Dust ◽  
House Dust Mite ◽  
Specific Immunotherapy ◽  
Dust Mite ◽  
Der P 1

Anti-IgD antibody attenuates collagen-induced arthritis by selectively depleting mature B-cells and promoting immune tolerance

2010 ◽  
Vol 35 (1) ◽  
pp. 86-97 ◽  
Author(s):  
Tue G. Nguyen ◽  
Christopher B. Little ◽  
Vanessa M. Yenson ◽  
Christopher J. Jackson ◽  
Sharon A. McCracken ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Tolerance ◽  
Collagen Induced Arthritis

scholarly journals Thrombospondin-1 (TSP1)-producing B Cells Restore Antigen (Ag)-specific Immune Tolerance in an Allergic Environment

2015 ◽  
Vol 290 (20) ◽  
pp. 12858-12867 ◽  
Author(s):  
Gui Yang ◽  
Xiao-Rui Geng ◽  
Zhi-Qiang Liu ◽  
Jiang-Qi Liu ◽  
Xiao-Yu Liu ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Tolerance ◽  
Thrombospondin 1

scholarly journals Immune Tolerance Developed in Platelet-Targeted FVIII Gene Therapy in Hemophilia Mice Is CD4+ T Cell-Mediated

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1071-1071
Author(s):  
Yingyu Chen ◽  
Xiaofeng Luo ◽  
Juan Chen ◽  
Jocelyn Schroeder ◽  
Christina K Baumgartner ◽  
...  
Keyword(s):  
Gene Therapy ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Immune Tolerance ◽  
Cd4 T Cells ◽  
Memory B Cells ◽  
Cd4 T Cell ◽  
Control Group

Abstract Immune response to factor VIII (FVIII) is not only a severe complication in protein replacement therapy, but also a major concern in gene therapy of hemophilia A. Our previous studies have demonstrated that platelet-targeted FVIII (2bF8) gene therapy together with in vivo drug-selection of transduced cells can not only rescue the bleeding diathesis but also induce anti-FVIII specific immune tolerance in FVIIInull mice. In the current study, we investigated 1) whether our non-selectable lentiviral vector (LV) for the induction of platelet-FVIII expression is sufficient to induce immune tolerance and 2) which cell compartment is tolerized after platelet gene therapy. Platelet-specific FVIII expression was introduced by 2bF8LV-transduction of hematopoietic stem cells followed by syngeneic transplantation into FVIIInull mice preconditioned with 660 cGy total body irradiation (TBI) or Busulfan (Bu) plus ATG (anti-thymocyte globulin). After bone marrow transplantation and reconstitution, animals were analyzed by PCR, qPCR, FVIII:C assay, and tail clipping test to confirm the success of 2bF8 gene therapy. Sixteen weeks after transplantation, animals were challenged with recombinant human FVIII (rhF8) via retro-orbital venous administration at a dose of 50 U/kg weekly for 4 weeks. The titers of anti-FVIII inhibitory antibodies (inhibitors) were determined by Bethesda assay. The CFSE-labeled CD4 T cell proliferation assay and ELISPOT-based memory B cell maturation assay were used to determine which cell compartment is tolerized to FVIII after 2bF8 gene therapy. The level of platelet-FVIII expression was 1.44 ± 0.39 mU/108 platelets (n = 6) in the 660 cGy group, which is not significantly different from the level obtained from the Bu+ATG group [3.04 ± 1.19 mU/108 platelets (n = 6)]. Even after rhF8 challenge, no antibodies were detected in 2bF8LV-transduced recipients in either group. In contrast, all animals in the control group that did not undergo gene therapy developed various levels of inhibitors (204±97 BU/ml, n=7). The frequency of regulatory T cells in both 660 cGy TBI (11.01±0.52%) and Bu+ATG (11.02±0.68%) groups were significantly higher than the control group (8.05±0.57%). T cell proliferation assay demonstrated that CD4+ T cells from 2bF8 LV-transduced recipients that had been challenged with rhF8 did not proliferate when restimulated with rhF8 in vitro. The daughter CD4+ T cells in the group with 10 U/ml of rhF8 were 5.84 ± 2.49% (n = 6), which was not significantly different from the control group without no rhF8 stimulation (0 U/ml) (5.33 ± 1.72%). CD4+ T cells from primed FVIIInull mice did proliferate after rhF8 restimulation. The proliferated daughter cell was 13.12 ± 6.76% (n = 7) in the group with rhF8 (10 U/ml) re-stimulation, which is significantly higher than the group without rhF8 co-culture (4.99 ± 1.16%). Since FVIII-specific memory B cell maturation is CD4+ T cell dependent, we isolated CD4+ T and memory B cells from 2bF8LV-transduced or FVIIInull mice after rhF8 immunization and co-cultured with rhF8 followed by ELISPOT assay to examine the antibody secreting cells. No spots were detected when memory B cells from rhF8-primed FVIIInull mice were co-cultured with CD4+ T cells from 2bF8LV-transduced recipients. In contrast, when memory B cells from either rhF8 immunized 2bF8LV-transduced or untreated FVIIInull mice were cultured with CD4+ T cells from rhF8-primed FVIIInull mice, there were 142 and 205 anti-FVIII antibody secreting cells, respectively, detected per 106 cells seeded. These results indicate that CD4+ T cells from 2bF8LV-transduced mice are tolerized to rhF8 stimulation. In conclusion, 2bF8 lentiviral gene transfer without in vivo selection of genetically manipulated cells can introduce FVIII-specific immune tolerance in hemophilia A mice and this immune tolerance is CD4+ T cell-mediated. Disclosures Baumgartner: Novo Nordisk: Research Funding. Shi:BloodCenter of Wisconsin: Patents & Royalties: METHOD OF INDUCING IMMUNE TOLERANCE THROUGH TARGETTED GENE EXPRESSION..

scholarly journals The Emerging Potentials of Human Regulatory B Cells Mediated Therapies in Myasthenia Gravis

2020 ◽  
Author(s):  
Md Rezaul Karim
Keyword(s):  
B Cells ◽  
Myasthenia Gravis ◽  
Immune Tolerance ◽  
Therapeutic Strategies ◽  
Regulatory B Cells ◽  
Chronic Infections ◽  
Pros And Cons ◽  
And Function ◽  
Negative Regulatory Role

Regulatory B cells (Bregs) with immunosuppressive function are critical in maintaining immune tolerance. In recent years, Bregs is an essential part of the study due to its therapeutic relevance and function in immune tolerance. The positive and negative regulatory role of human Bregs in immune tolerance is being discussed in several pathologies, including in autoimmune diseases, cancers, chronic infections, strokes in multiple reports. The negative regulatory roles of human Bregs are associated with lesser numbers and functional abnormalities in most of these studies, including myasthenia gravis (MG). In this review, the potential findings regarding human Bregs in MG, and Bregs mediated potential therapeutic strategies with its pros and cons have been discussed based on previous and current reports.

scholarly journals Mechanisms of allergen-specific B cell tolerance in children with cow’s milk-oral immunotherapy and natural outgrowth of milk allergy

2021 ◽  
Author(s):  
Pattraporn Satitsuksanoa ◽  
Willem van de Veen ◽  
Ge Tan ◽  
Oliver Wirz ◽  
Kirstin Jansen ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Tolerance ◽  
Oral Immunotherapy ◽  
Essential Elements ◽  
Cow’S Milk ◽  
Milk Allergy ◽  
Allergen Specific Immunotherapy ◽  
Cow's Milk ◽  
Clinical Healing ◽  
Natural Tolerance

Abstract Antigen-specific memory B cells play a key role in the induction of immune tolerance to food allergens and clinical healing. Here, we characterized the role of allergen-specific B cells in immune tolerance induced by oral allergen-specific immunotherapy (OIT) and natural tolerance that developed in children who spontaneously outgrew cow’s milk allergy. Increased frequency of circulating milk allergen αS1-casein -specific B cells was observed after OIT and natural tolerance (NT). Milk desensitized subjects showed partial acquisition of tolerance phenotypic features induced tolerance, suggesting that desensitization is an earlier stage of tolerance. Immunoregulatory genes such as IL10RA and IGHG4 are significantly upregulated after OIT (desensitized and tolerance) versus NT. Secreted proteins from allergen-specific B cells revealed higher amounts of regulatory cytokines, IL-10 and TGF-β after OIT and NT. Taken together, allergen-specific B cells are essential elements in regulating food allergen tolerance in both OIT-received and naturally-resolved individuals.

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