CRTC2 regulates plasma cell metabolism and survival

Antibody secreting cell (ASC) function and longevity determines the strength and durability of a humoral immune response. Previously, we identified the inactivation of the CREB-regulated transcriptional coactivator-2 (CRTC2) in an in vitro B cell differentiation assay that produced functional ASCs. However, the requirement for CRTC2 inactivation in ASC physiology in vivo remains unknown. Using transgenic (TG) mice that express a constitutively active form of CRTC2 (Crtc2-AA) as an experimental tool, we demonstrate that Crtc2 repression in plasma cells (PCs) is an intrinsic requirement for ASC metabolic fitness. Sustained CRTC2 activity shortens the survival of splenic and bone marrow PCs, resulting in reduced numbers of long-lived PCs and antibody deficits against T cell dependent and independent antigens, and an acute viral infection. TG PCs resemble short-lived PCs with reductions in glycolysis, oxidative metabolism, spare respiratory capacity, and antibody secretion. Mechanistically, Crtc2 repression is necessary for the fidelity of PC gene expression and mRNA alternative-splicing programs. Combined, Crtc2 repression in PCs must occur to support PC metabolism and extend ASC survival during a humoral immune response.

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Colloidal manganese salt improves the efficacy of rabies vaccines in mice, cats, and dogs

Journal of Virology ◽

10.1128/jvi.01414-21 ◽

2021 ◽

Author(s):

Zongmei Wang ◽

Yueming Yuan ◽

Chen Chen ◽

Chengguang Zhang ◽

Fei Huang ◽

...

Keyword(s):

Immune Response ◽

B Cells ◽

Humoral Immune Response ◽

Plasma Cells ◽

Vaccine Development ◽

Type I ◽

Humoral Immune ◽

Tfh Cells

Rabies, caused by rabies virus (RABV), remains a serious threat to public health in most countries worldwide. At present, the administration of rabies vaccines has been the most effective strategy to control rabies. Herein, we evaluate the effect of colloidal manganese salt (Mn jelly, MnJ) as an adjuvant of rabies vaccine in mice, cats, and dogs. The results showed that MnJ promoted type I interferon (IFN-I) and cytokine production in vitro and the maturation of dendritic cells (DCs) in vitro and in vivo . Besides, MnJ serving as an adjuvant for rabies vaccines could significantly facilitate the generation of T follicular helper (Tfh) cells, germinal center (GC) B cells, plasma cells (PCs), and RABV-specific antibody-secreting-cells (ASCs), consequently improved the immunogenicity of rabies vaccines and provide better protection against virulent RABV challenge. Similarly, MnJ enhanced the humoral immune response in cats and dogs as well. Collectively, our results suggest that MnJ can facilitate the maturation of DCs during rabies vaccination, which can be a promising adjuvant candidate for rabies vaccines. IMPORTANCE Extending humoral immune response by using adjuvants is an important strategy for vaccine development. In this study, a novel adjuvant MnJ supplemented in rabies vaccines was evaluated in mice, cats, and dogs. Our results in the mouse model revealed that MnJ increased the numbers of mature DCs, Tfh cells, GC B cells, PCs, and RABV-specific ASCs, resulting in enhanced immunogenicity and protection rate of rabies vaccines. We further found MnJ had the same stimulative effect in cats and dogs. Our study provides the first evidence that MnJ serving as a novel adjuvant of rabies vaccines can boost immune response both in a mouse and pet model.

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Induction of a Specific Humoral Immune Response by Nasal Delivery of Bcla2ctd of Clostridioides difficile

International Journal of Molecular Sciences ◽

10.3390/ijms21041277 ◽

2020 ◽

Vol 21 (4) ◽

pp. 1277 ◽

Cited By ~ 3

Author(s):

Ana Raquel Maia ◽

Rodrigo Reyes-Ramírez ◽

Marjorie Pizarro-Guajardo ◽

Anella Saggese ◽

Pablo Castro-Córdova ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Surface Protein ◽

Developed Countries ◽

Nasal Delivery ◽

Experimental Conditions ◽

Humoral Immune ◽

Clostridioides Difficile

Clostridioides difficile, formerly known as Clostridium difficile, is a spore-forming bacterium considered as the most common cause of nosocomial infections in developed countries. The spore of C. difficile is involved in the transmission of the pathogen and in its first interaction with the host; therefore, a therapeutic approach able to control C. difficile spores would improve the clearance of the infection. The C-terminal (CTD) end of BclA2, a spore surface protein of C. difficile responsible of the interaction with the host intestinal cells, was selected as a putative mucosal antigen. The BclA2 fragment, BclA2CTD, was purified and used to nasally immunize mice both as a free protein and after adsorption to the spore of Bacillus subtilis, a well-established mucosal delivery vehicle. While the adsorption to spores increased the in vitro stability of BclA2CTD, in vivo both free and spore-adsorbed BclA2CTD were able to induce a similar, specific humoral immune response in a murine model. Although in the experimental conditions utilized the immune response was not protective, the induction of specific IgG indicates that free or spore-bound BclA2CTD could act as a putative mucosal antigen targeting C. difficile spores.

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l-carnitine modifies the humoral immune response in mice after in vitro or in vivo treatment

International Immunopharmacology ◽

10.1016/s1567-5769(01)00105-9 ◽

2001 ◽

Vol 1 (9-10) ◽

pp. 1813-1822 ◽

Cited By ~ 33

Author(s):

I. Athanassakis ◽

M. Mouratidou ◽

P. Sakka ◽

A. Evangeliou ◽

M. Spilioti ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Humoral Immune ◽

In Vivo Treatment

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The immunoregulatory effects of edeine analogues in mice

Cellular & Molecular Biology Letters ◽

10.2478/s11658-006-0061-z ◽

2007 ◽

Vol 12 (2) ◽

Cited By ~ 4

Author(s):

Zbigniew Czajgucki ◽

Michał Zimecki ◽

Ryszard Andruszkiewicz

Keyword(s):

Immune Response ◽

Cell Proliferation ◽

Humoral Immune Response ◽

Delayed Type Hypersensitivity ◽

Pokeweed Mitogen ◽

Splenocyte Proliferation ◽

Humoral Immune ◽

Immune Response In Vitro

AbstractThe edeines analogs were tested in several in vitro and in vivo assays using the mouse model, with edeine B (peptide W1) and cyclosporine A as reference compounds. The peptides displayed moderate, stimulatory effects on concanavalin A-induced (ConA-induced) splenocyte proliferation, whereas their effects on pokeweed mitogen-induced (PWM-induced) splenocyte proliferation were inhibitory. The peptides inhibited lipopolysacharide-induced (LPS-induced) tumor necrosis factor alpha production but had little effect on interleukin 6 production. In the model of the humoral immune response in vitro to sheep red blood cells, peptide 1 was distinctly stimulatory in the investigated concentrations (1-100 μg/ml), whereas peptides 3 and 4 only stimulated the number of antibody-forming cells at the highest concentration (100 μg/ml). In the model of the delayed type hypersensitivity in vivo to ovalbumin, the peptides were moderately suppressive (3 being the most active). The reference peptide W1 stimulated ConA-induced cell proliferation at 1–10 μg/ml but was inhibitory at 100 μg/ml. It also inhibited PWM-induced cell proliferation in a dose-dependent manner. This peptide had no effect on the humoral immune response in vitro or on cytokine production, but inhibited DTH reaction in vivo. The relationship between structure and activity, and a possible mode of action of the peptides, is discussed in this paper.

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Influence of introduction of interleukin-2 and interleukin-12 into experimental marker DNA-vaccine

Faktori eksperimental'noi evolucii organizmiv ◽

10.7124/feeo.v25.1158 ◽

2019 ◽

Vol 25 ◽

pp. 160-165

Author(s):

Ia. O. Pokholenko ◽

T. P. Gulko ◽

V. A. Kordium

Keyword(s):

Immune Response ◽

Dna Vaccine ◽

Humoral Immune Response ◽

Interleukin 2 ◽

Classical Swine Fever ◽

Interleukin 12 ◽

Chimeric Proteins ◽

Humoral Immune

Aim. To determine the effects of the combined administration of recombinant expression vectors containing genes of murine interleukin-2 and interleukin-12 on humoral immune response, elicited by the experimental marker DNA-vaccine against classical swine fever. Methods. Expression of chimeric proteins in vitro and in vivo was determined by western-blot analysis. The antibodies specific to target antigens in blood serum have been detected by ELISA. Results. A series of recombinant plasmid vectors containing the genes of murine interleukin-2 and chimeric murine interleukin-12 have been developed. It has been shown that target chimeric proteins were expressed from the developed vectors both in vitro in HEK293 and in vivo in murine muscle tissue. The use of combined administration of murine interleukin-2 and interleukin-12 genes resulted in significant enhancement of titer of the anti-E2 and anti-β-galactosidase IgG, induced by vaccination with experimental marker DNA-vaccine against CSF, and model DNA-vaccine respectively. Conclusions. The data obtained show that the introduction of recombinant expressing vectors containing genes of murine interleukin-2 and interleukin-12 into vaccine preparations enhances humoral immune response elicited by the experimental marker DNA-vaccine against CSF and modelDNA-vaccine. Keywords: DNA-vaccine, humoral immune response, interleukin-2, interleukin-12, classical swine fever.

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Histone methyltransferase DOT1L controls state-specific identity during B cell differentiation

10.1101/826370 ◽

2019 ◽

Cited By ~ 1

Author(s):

Muhammad Assad Aslam ◽

Mir Farshid Alemdehy ◽

Eliza Mari Kwesi-Maliepaard ◽

Marieta Caganova ◽

Iris N. Pardieck ◽

...

Keyword(s):

Cell Differentiation ◽

B Cells ◽

B Cell ◽

Cell Fate ◽

Plasma Cell ◽

Plasma Cells ◽

B Cell Differentiation ◽

Humoral Immune

AbstractDifferentiation of naïve peripheral B cells into terminally differentiated plasma cells is characterized by epigenetic alterations, yet the epigenetic mechanisms that control B cell fate remain unclear. Here we identified a central role for the histone H3K79 methyltransferase DOT1L in controlling B cell differentiation. Murine B cells lacking Dot1L failed to establish germinal centers (GC) and normal humoral immune responses in vivo. In vitro, activated B cells showed aberrant differentiation and prematurely acquired plasma cell features. Mechanistically, combined epigenomics and transcriptomics analysis revealed that DOT1L promotes expression of a pro-proliferative, pro-GC program. In addition, DOT1L supports the repression of an anti-proliferative, plasma cell differentiation program by maintaining expression of the H3K27 methyltransferase Ezh2, the catalytic component of Polycomb Repressor Complex 2 (PRC2). Our findings show that DOT1L is a central modulator of the core transcriptional and epigenetic landscape in B cells, establishing an epigenetic barrier that warrants B cell naivety and GC B cell differentiation.

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Norepinephrine and serotonin content of the murine spleen: Its relationship to lymphocyte β-adrenergic receptor density and the humoral immune response in vivo and in vitro

Cellular Immunology ◽

10.1016/0008-8749(88)90123-2 ◽

1988 ◽

Vol 117 (2) ◽

pp. 339-351 ◽

Cited By ~ 71

Author(s):

Bruce A. Fuchs ◽

Kerry S. Campbell ◽

Albert E. Munson

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Adrenergic Receptor ◽

Receptor Density ◽

Serotonin Content ◽

Humoral Immune ◽

Murine Spleen

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The effect of the antiherpesvirus drug 5-methoxymethyl-2′-deoxyuridine on the humoral immune response in vivo

Canadian Journal of Microbiology ◽

10.1139/m77-158 ◽

1977 ◽

Vol 23 (8) ◽

pp. 1059-1061 ◽

Cited By ~ 4

Author(s):

Barry T. Rouse ◽

Lorne A. Babiuk ◽

V. Sagar Gupta

Keyword(s):

Immune Response ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Antiviral Activity ◽

Immune Responses ◽

Humoral Immune Response ◽

Humoral Immune ◽

Simplex Virus

5-Methoxymethyl-2′-deoxyuridine (MMUdR), a drug with potent antiviral activity in vitro against Herpes simplex virus, was investigated for its immunosuppressive effects. Doses as high as 2000 mg/kg given daily for 9 days were not immunosuppressive as judged by the fact that treated animals produced normal immune responses to sheep erythrocytes, Brucella bacteria, and Herpes simplex virus.

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