Reactivation of IgG-switched memory B cells by BCR-intrinsic signal amplification promotes IgG antibody production

Immunostimulants are greatly required for the upregulation of immunity to fight against viral and bacterial infections and cancers. Bell peppers (Capsicum annuum L.), eaten as vegetables, are rich sources of vitamin C and E, provitamin A, β-carotene, and numerous phenolic compounds. Antimicrobial, antioxidant, anti-mutagenic and anti-inflammatory properties of Bell peppers were reported. Our research group for the first time reported the immunomodulatory activities of Bell peppers. In this study, we evaluated the antibody production abilities of two different colored Bell peppers (red and green) in the culture of antibody producing splenic B cells of mice. Antibodies and the number of viable cells were determined by an ELISA and MTT assays, respectively. Red Bell pepper Extract (RBPE) at the doses of (0.375, 0.75, 1.5, and 2.25 mg/mL) significantly augmented the production of polyclonal IgM and IgG antibodies in-vitro. The highest amount of IgM antibody production was observed by the dose of 1.5 mg/kg which was 3 times higher than that of the untreated cells. Similarly, RBPE also enhanced the production of IgG antibody in the culture of murine splenic B cells. On the contrary, cultural treatment of murine splenic B cells with Green Bell pepper Extract (GBPE) could not stimulate the B cells, and hence, failed to produce neither IgM nor IgG antibody. Thus the current findings suggest that consumption of Red Bell Pepper extract or its vegetables, not green pepper, may be beneficial to strengthen humoral immune responses. Bangladesh Pharmaceutical Journal 24(1): 45-53, 2021

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Virus-specific IgM and IgG Antibody Production by B Cells during Herpes Simplex Virus Type 2-induced Immunosuppression as Analysed by an Immunospot Assay

Journal of General Virology ◽

10.1099/0022-1317-68-7-1951 ◽

1987 ◽

Vol 68 (7) ◽

pp. 1951-1959 ◽

Cited By ~ 4

Author(s):

S. Nick ◽

B. Metzger ◽

S. Muller ◽

D. Falke

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

B Cells ◽

Virus Type ◽

Antibody Production ◽

Herpes Simplex Virus Type ◽

Igg Antibody ◽

Simplex Virus

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THU0041 IFNΑ AND IL21 PROMOTE DISTINCT POPULATIONS OF EFFECTOR B CELLS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5752 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 233.2-234

Author(s):

M. Boudigou ◽

A. Grasseau ◽

N. Chriti ◽

J. O. Pers ◽

L. Le Pottier ◽

...

Keyword(s):

T Cells ◽

B Cells ◽

B Cell ◽

Antibody Production ◽

Lupus Erythematosus ◽

Memory B Cells ◽

Molecular Profile ◽

B Cell Differentiation ◽

Regulatory B Cells ◽

Effector Functions

Background:B cells play a crucial role in the pathogenesis of systemic autoimmunity through various effector functions, including auto-antibody production, secretion of pro-inflammatory cytokines and antigen presentation to T cells. Interferon alpha (IFNα), mainly produced by innate cells (Menon et al., 2016), and interleukin (IL)-21 which is secreted by follicular helper T cells (Berglund et al., 2013), promote the generation of auto-reactive IgG-secreting plasma cells. However, it is suggested that IFNα participate also to the generation of regulatory B cells.Objectives:To further understand the disturbing microenvironmental signals leading to autoimmune diseases, we aim to define a coherent framework integrating the B-cell subsets having different ability to respond to microenvironmental signals, and the signalling pathways driving the differentiation and the functional fate of B cells.Methods:Naïve and several populations of memory B cells were isolated from peripheral blood of healthy donors and differentiatedin vitroin the presence of IL21 or IFNα. The phenotype and the expression of transcription factors were analysed by flow cytometry and molecular identity of these cells was further determined by transcriptomic approaches. Functional analyses were performed to assess the effector functions of B cells and their potential regulatory effects on T cells.Results:IFNα, in synergy with CpG, promote the generation of CD27highCD38highplasmablasts (PB), mainly arising from memory subsets, but not IL21. However, IFNα and IL21 induce the transcriptional program of B-cell differentiation by up-regulating IRF4 and Blimp1 expression. Unlike IFNα, IL21 drive the expansion of CD11c+T-bet+cells only from switched memory subsets, suggesting T-bet may be a footprint of long-lived memory B cells.Even though subtle differences were observed in the antibody production between IFNα and IL21-stimulated memory B cells, naïve cells secreted less amount of IgM and IL10 when stimulated with IL21.Transcriptomic studies are still in progress to further define the molecular profile of those distinct effector B cells.Conclusion:Taken together, these findings suggest that IFNα promote a rapid differentiation of B cells into IL10 and Ig-secreting PB whereas IL21 contributes to the generation of T-bet+atypical pre-PB that may have a role in chronic autoimmune disorders.References:[1]Berglund, L.J., Avery, D.T., Ma, C.S., Moens, L., Deenick, E.K., Bustamante, J., Boisson-Dupuis, S., Wong, M., Adelstein, S., Arkwright, P.D., et al. (2013). IL-21 signalling via STAT3 primes human naive B cells to respond to IL-2 to enhance their differentiation into plasmablasts. Blood122, 3940–3950.[2]Menon, M., Blair, P.A., Isenberg, D.A., and Mauri, C. (2016). A Regulatory Feedback between Plasmacytoid Dendritic Cells and Regulatory B Cells Is Aberrant in Systemic Lupus Erythematosus. Immunity44, 683–697.Disclosure of Interests:None declared

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Mechanistic insights into the impairment of memory B cells and antibody production in the elderly

AGE ◽

10.1007/s11357-011-9371-9 ◽

2012 ◽

Vol 35 (2) ◽

pp. 371-381 ◽

Cited By ~ 25

Author(s):

Judith H. Aberle ◽

Karin Stiasny ◽

Michael Kundi ◽

Franz X. Heinz

Keyword(s):

B Cells ◽

Antibody Production ◽

The Elderly ◽

Memory B Cells

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Toll-Like Receptor Homolog CD180 Expression Is Diminished on Natural Autoantibody-Producing B Cells of Patients with Autoimmune CNS Disorders

Journal of Immunology Research ◽

10.1155/2021/9953317 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Zsófia Hayden ◽

Szabina Erdő-Bonyár ◽

Beáta Bóné ◽

Noémi Balázs ◽

Kornélia Bodó ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Peripheral Blood ◽

Bacterial Infections ◽

Citrate Synthase ◽

Memory B Cells ◽

Igg Antibody ◽

Autoantibody Production ◽

B Cell Subsets ◽

Natural Autoantibody

Purpose. Decreased expression of TLR homolog CD180 in peripheral blood B cells and its potential role in antibody production have been described in autoimmune diseases. Effectiveness of anti-CD20 therapy in neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) strengthens the role of B cells in the pathogenesis. Therefore, we aimed to investigate the CD180 expression of peripheral blood B cell subsets in NMOSD and MS patients and analyze the levels of natural anti-citrate synthase (CS) IgG autoantibodies and IgG antibodies induced by bacterial infections reported to play a role in the pathogenesis of NMOSD or MS. Methods. We analyzed the distribution and CD180 expression of peripheral blood B cell subsets, defined by CD19/CD27/IgD staining, and measured anti-CS IgM/G natural autoantibody and antibacterial IgG serum levels in NMOSD, RRMS, and healthy controls (HC). Results. We found decreased naïve and increased memory B cells in NMOSD compared to MS. Among the investigated four B cell subsets, CD180 expression was exclusively decreased in CD19+CD27+IgD+ nonswitched (NS) memory B cells in both NMOSD and MS compared to HC. Furthermore, the anti-CS IgM natural autoantibody serum level was lower in both NMOSD and MS. In addition, we found a tendency of higher anti-CS IgG natural autoantibody levels only in anti-Chlamydia IgG antibody-positive NMOSD and MS patients. Conclusions. Our results suggest that reduced CD180 expression of NS B cells could contribute to the deficient natural IgM autoantibody production in NMOSD and MS, whereas natural IgG autoantibody levels show an association with antibacterial antibodies.

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Splenectomized Patients Have Reduced CD27+ Memory B Cells but Protective Antibody Responses to Pneumococcal Vaccination.

Blood ◽

10.1182/blood.v104.11.3025.3025 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3025-3025

Author(s):

Heather A. Wasserstrom ◽

Charlotte Cunningham-Rundles ◽

Lony C.L. Lim ◽

Nadia T. Guerrero ◽

Megan H. Wissert ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Pneumococcal Vaccine ◽

Pneumococcal Vaccination ◽

Memory B Cells ◽

Antibody Responses ◽

Igg Antibody ◽

Female Age ◽

Post Vaccination ◽

Conjugate Pneumococcal Vaccine

Abstract Introduction : Splenectomized patients are thought to have poor antibody responses to polyvalent non-conjugate pneumococcal vaccination. Recent studies found that these patients have decreased circulating CD27+ (memory) B cells, suggesting the possibility of a specific defect in splenectomized patients’ humoral immunity. In this study we sought to verify this reduction and ascertain whether it correlates with inadequate antibody production. Thus, we enumerated peripheral blood CD27+ B cells in splenectomized patients and non-splenectomized controls, administered a polyvalent non-conjugate pneumococcal vaccine, and compared their IgG antibody titers to all 23 serotypes before and 4 to 6 weeks after immunization. Participants : 31 participants were enrolled: 21 splenectomized patients (6 male, 15 female; age: 10–80 years, mean: 47.3) and 10 non-splenectomized controls (2 male, 8 female; age: 26–64 years, mean: 37.5). Indications for splenectomy included ITP (17), spherocytosis (2), hemolytic anemia (1), and thrombocytopenia-absent radii syndrome (1). No patients received pneumococcal vaccination within 2 years, or IVIG, Rituxan or immunosuppressive therapy within 6 months of enrollment. Time since splenectomy ranged from 6 months to 50 years (mean: 12.5). 17 patients received at least one prior pneumococcal immunization, from 3 to 22 years previously (mean: 8.0). No controls formerly received a pneumococcal vaccination. Results : B Cell Enumeration: Compared to the 10 controls, the 21 splenectomized patients had a greater percentage of circulating B cells (patients: 12.05% ± 7.61; controls: 7.99% ± 2.92; ρ = 0.042), but a significantly reduced CD27+ B cell component (patients: 12.38% ± 8.48; controls: 40.46% ± 18.68; ρ = 0.001). This reduction was not specific to either of the CD27+ B cell populations (IgM+IgD+CD27+: patients: 31.64% ± 19.72; controls: 44.58% ± 16.01; ρ = 0.081. IgM−IgD−CD27+: patients: 52.05 ± 23.71; controls: 48.08% ± 13.89; ρ = 0.628.) Antibody Analysis: Antibody responses to pneumococcal vaccination did not differ significantly between splenectomized patients and non-splenectomized controls. 9 of 13 splenectomized patients and 9 of 10 controls achieved protection to immunization (χ2 = 1.433; ρ = 0.339), defined as a post-vaccination IgG titer ≥ 1.3 μg/ml or a post:pre-vaccination titer ratio ≥ 4, in at least 70% of the serotypes tested (~16 of 23 serotypes). When comparing the mean number of serotypes to which each cohort achieved protection, splenectomized patients and controls mounted statistically similar responses, at 17 and 20 serotypes, respectively (ρ = 0.134). Furthermore, the geometric means of each cohort’s post-vaccination IgG titers did not differ significantly in 22 of the 23 serotypes. Conclusion : Splenectomized patients had a significant reduction in their circulating CD27+ B cells. This decrease did not correlate with an impaired antibody response to (re-)immunization with a polyvalent non-conjugate pneumococcal vaccine however, as splenectomized patients and non-splenectomized controls achieved comparable protection and produced similar IgG responses to vaccination. For ITP patients and others who have undergone splenectomy, our data indicates that a pneumococcal vaccine can be effectively administered after splenectomy, if needed.

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