scholarly journals Notch2-dependent DC2s mediate splenic germinal center responses

2018 ◽  
Vol 115 (42) ◽  
pp. 10726-10731 ◽  
Author(s):  
Carlos G. Briseño ◽  
Ansuman T. Satpathy ◽  
Jesse T. Davidson ◽  
Stephen T. Ferris ◽  
Vivek Durai ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mhc Class Ii ◽  
T Cell Activation ◽  
Humoral Immunity ◽  
Germinal Center ◽  
Cell Activation ◽  
Cell Formation ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Follicular Helper

CD4+ T follicular helper (TFH) cells support germinal center (GC) reactions promoting humoral immunity. Dendritic cell (DC) diversification into genetically distinct subsets allows for specialization in promoting responses against several types of pathogens. Whether any classical DC (cDC) subset is required for humoral immunity is unknown, however. We tested several genetic models that selectively ablate distinct DC subsets in mice for their impact on splenic GC reactions. We identified a requirement for Notch2-dependent cDC2s, but not Batf3-dependent cDC1s or Klf4-dependent cDC2s, in promoting TFH and GC B cell formation in response to sheep red blood cells and inactivated Listeria monocytogenes. This effect was mediated independent of Il2ra and several Notch2-dependent genes expressed in cDC2s, including Stat4 and Havcr2. Notch2 signaling during cDC2 development also substantially reduced the efficiency of cDC2s for presentation of MHC class II-restricted antigens, limiting the strength of CD4 T cell activation. Together, these results demonstrate a nonredundant role for the Notch2-dependent cDC2 subset in supporting humoral immune responses.

scholarly journals Cellular and humoral immune responses associated with protection in sheep vaccinated against Teladorsagia circumcincta

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Cynthia Machín ◽  
Yolanda Corripio-Miyar ◽  
Julia N. Hernández ◽  
Tara Pérez-Hernández ◽  
Adam D. Hayward ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Anthelmintic Resistance ◽  
Gastrointestinal Nematodes ◽  
Control Group ◽  
Sheep Breeds ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Teladorsagia Circumcincta

AbstractDue to increased anthelmintic resistance, complementary methods to drugs are necessary to control gastrointestinal nematodes (GIN). Vaccines are an environmentally-friendly and promising option. In a previous study, a Teladorsagia circumcincta recombinant sub-unit vaccine was administered to two sheep breeds with different levels of resistance against GIN. In the susceptible Canaria Sheep (CS) breed, vaccinates harboured smaller worms with fewer eggs in utero than the control group. Here, we extend this work, by investigating the cellular and humoral immune responses of these two sheep breeds following vaccination and experimental infection with T. circumcincta. In the vaccinated CS group, negative associations between antigen-specific IgA, IgG2 and Globule Leukocytes (GLs) with several parasitological parameters were established as well as a higher CD4+/CD8+ ratio than in control CS animals, suggesting a key role in the protection induced by the vaccine. In the more resistant Canaria Hair Breed (CHB) sheep the vaccine did not significantly impact on the parasitological parameters studied and none of these humoral associations were observed in vaccinated CHB lambs, although CHB had higher proportions of CD4+ and CD8+ T cells within the abomasal lymph nodes, suggesting higher mucosal T cell activation. Each of the component proteins in the vaccine induced an increase in immunoglobulin levels in vaccinated groups of each breed. However, levels of immunoglobulins to only three of the antigens (Tci-MEP-1, Tci-SAA-1, Tci-ASP-1) were negatively correlated with parasitological parameters in the CS breed and they may be, at least partially, responsible for the protective effect of the vaccine in this breed. These data could be useful for improving the current vaccine prototype.

scholarly journals Recombinant Rabies Virus Overexpressing OX40-Ligand Enhances Humoral Immune Responses by Increasing T Follicular Helper Cells and Germinal Center B Cells

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 144 ◽  
Author(s):  
Yingying Li ◽  
Ling Zhao ◽  
Baokui Sui ◽  
Zhaochen Luo ◽  
Yachun Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
Rabies Virus ◽  
Germinal Center ◽  
Rabies Vaccine ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Follicular Helper ◽  
Ox40 Ligand

Rabies, caused by the rabies virus (RABV), remains a serious threat to public health in most countries. Development of a single-dose and efficacious rabies vaccine is the most important method to restrict rabies virus transmission. Costimulatory factor OX40-ligand (OX40L) plays a crucial role in the T cell-dependent humoral immune responses through T-B cell interaction. In this work, a recombinant RABV overexpressing mouse OX40L (LBNSE-OX40L) was constructed, and its effects on immunogenicity were evaluated in a mouse model. LBNSE-OX40L-immunized mice generated a larger number of T follicular helper (Tfh) cells, germinal center (GC) B cells, and plasma cells (PCs) than the parent virus LBNSE-immunized mice. Furthermore, LBNSE-OX40L induced significantly higher levels of virus-neutralizing antibodies (VNA) as early as seven days post immunization (dpi), which lasted for eight weeks, resulting in better protection for mice than LBNSE (a live-attenuated rabies vaccine strain). Taken together, our data in this study suggest that OX40L can be a novel and potential adjuvant to improve the induction of protective antibody responses post RABV immunization by triggering T cell-dependent humoral immune responses, and that LBNSE-OX40L can be developed as an efficacious and nonpathogenic vaccine for animals.

Antigen targeting to splenic CD169+ macrophages induces strong humoral immune responses and CD4+ T cell activation

2012 ◽  
Vol 51 (1) ◽  
pp. 12-13
Author(s):  
Henrike Veninga ◽  
Ellen Borg ◽  
Hakan Kalay ◽  
Yvette van Kooyk ◽  
Georg Kraal ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals CD8α− Dendritic Cells Induce Antigen-Specific T Follicular Helper Cells Generating Efficient Humoral Immune Responses

Cell Reports ◽  
2015 ◽  
Vol 11 (12) ◽  
pp. 1929-1940 ◽  
Author(s):  
Changsik Shin ◽  
Jae-A Han ◽  
Hyein Koh ◽  
Bongseo Choi ◽  
Yongbin Cho ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
T Follicular Helper Cells ◽  
Humoral Immune ◽  
Helper Cells ◽  
Humoral Immune Responses ◽  
Follicular Helper

scholarly journals PPARγ Negatively Regulates T Cell Activation to Prevent Follicular Helper T Cells and Germinal Center Formation

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e99127 ◽  
Author(s):  
Hong-Jai Park ◽  
Do-Hyun Kim ◽  
Jin-Young Choi ◽  
Won-Ju Kim ◽  
Ji Yun Kim ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Germinal Center ◽  
Cell Activation ◽  
Helper T Cells ◽  
Follicular Helper T Cells ◽  
Follicular Helper ◽  
Germinal Center Formation

scholarly journals Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance

2014 ◽  
Vol 112 (2) ◽  
pp. E156-E165 ◽  
Author(s):  
Roberto A. Maldonado ◽  
Robert A. LaMothe ◽  
Joseph D. Ferrari ◽  
Ai-Hong Zhang ◽  
Robert J. Rossi ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Coagulation Factor ◽  
Immunological Tolerance ◽  
Immunosuppressive Drugs ◽  
Free Form ◽  
Peptide Antigens ◽  
Humoral Immune ◽  
Novel Approach

Current treatments to control pathological or unwanted immune responses often use broadly immunosuppressive drugs. New approaches to induce antigen-specific immunological tolerance that control both cellular and humoral immune responses are desirable. Here we describe the use of synthetic, biodegradable nanoparticles carrying either protein or peptide antigens and a tolerogenic immunomodulator, rapamycin, to induce durable and antigen-specific immune tolerance, even in the presence of potent Toll-like receptor agonists. Treatment with tolerogenic nanoparticles results in the inhibition of CD4+ and CD8+ T-cell activation, an increase in regulatory cells, durable B-cell tolerance resistant to multiple immunogenic challenges, and the inhibition of antigen-specific hypersensitivity reactions, relapsing experimental autoimmune encephalomyelitis, and antibody responses against coagulation factor VIII in hemophilia A mice, even in animals previously sensitized to antigen. Only encapsulated rapamycin, not the free form, could induce immunological tolerance. Tolerogenic nanoparticle therapy represents a potential novel approach for the treatment of allergies, autoimmune diseases, and prevention of antidrug antibodies against biologic therapies.

scholarly journals Essential Function for the Nuclear Protein Akirin2 in B Cell Activation and Humoral Immune Responses

2015 ◽  
Vol 195 (2) ◽  
pp. 519-527 ◽  
Author(s):  
Sarang Tartey ◽  
Kazufumi Matsushita ◽  
Tomoko Imamura ◽  
Atsuko Wakabayashi ◽  
Daisuke Ori ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Cell Activation ◽  
Nuclear Protein ◽  
B Cell Activation ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Essential Function

scholarly journals The in vivo function of a noncanonical TRAF2-binding domain in the C-terminus of CD40 in driving B-cell growth and differentiation

Blood ◽  
2007 ◽  
Vol 110 (1) ◽  
pp. 193-200 ◽  
Author(s):  
Li-Fan Lu ◽  
Cory L. Ahonen ◽  
Evan F. Lind ◽  
Vanitha S. Raman ◽  
W. James Cook ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Cell Activation ◽  
Affinity Maturation ◽  
Functional Domain ◽  
Antibody Isotype ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cell Immunity

The recruitment of tumor necrosis factor receptor–associated factors (TRAFs) 1, 2, 3, 5, and 6 to the CD40 cytoplasmic tail upon CD40 trimerization results in downstream signaling events that ultimately lead to CD40-dependent, thymus-dependent (TD) humoral immune responses. Previously, we have shown signaling through the C-terminal tail of CD40 in the absence of canonical TRAF-binding sites is capable of signaling through an alternative TRAF2-binding site. Here, we demonstrate that B cells from mice harboring CD40 with only the C-terminal tail can activate both canonical and noncanonical NFκB signaling pathways. Moreover, while lacking germinal center formation, several hallmarks of humoral immune responses including clonal B-cell activation/expansion, antibody isotype switching, and affinity maturation remain normal. This study demonstrates a new functional domain in CD40 that controls critical aspects of B-cell immunity in an in vivo setting.

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