scholarly journals B-cell dynamics during experimental endotoxemia in humans

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Alexandra Brinkhoff ◽  
Ye Zeng ◽  
Annette Sieberichs ◽  
Sebastian Dolff ◽  
Xu Shilei ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Immune Dysfunction ◽  
Memory B Cells ◽  
Cell Dynamics ◽  
Human Endotoxemia ◽  
Lps Challenge ◽  
Cell Immunity ◽  
Endotoxemia Model ◽  
The Impact

Abstract Recently, B cells with regulatory functions suppressing T-cell immunity were identified. Inflammation in the context of sepsis is characterized by a profound immune dysfunction increasing the patient’s risk for additional infections. The impact of endotoxemia on B-cell dynamics, regulatory B cells (Breg) and its contribution to immune dysfunction is unknown. It is the aim of the present study to characterize the dynamics of the B-cell compartment and Breg in an experimental human endotoxemia model. In this randomized placebo-controlled cross-over study, 20 healthy males received an intravenous injection of endotoxin (Escherichia coli lipopolysaccharide, LPS, 0.8 ng/kg body weight) or placebo (saline 0.9%) on two otherwise identical study days. B cells were analyzed by flow cytometry at baseline and repeatedly up to 72 h after endotoxin/placebo injection. Absolute CD19+ B cells counts showed a significant decrease 3 h after endotoxin injection. Memory B cells were partially depleted from the circulation; the total number of Breg was significantly diminished 3 h after LPS challenge. Production of anti-inflammatory interleukin (IL)-10 (IL-10) by Breg was unaltered after LPS challenge. Systemic B-cell activating factor (BAFF) levels were significantly increased with a maximum after 24 h and remained increased up to 72 h post-injection. Endotoxemia causes a transient depletion of memory B cells and Breg from the circulation. However, the functional capacity of B cells to produce IL-10 is not impaired.

Vaccine-elicited CD4 T cells prevent the deletion of antiviral B cells in chronic infection

2021 ◽  
Vol 118 (46) ◽  
pp. e2108157118
Author(s):  
Kerstin Narr ◽  
Yusuf I. Ertuna ◽  
Benedict Fallet ◽  
Karen Cornille ◽  
Mirela Dimitrova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Memory B Cells ◽  
Type I ◽  
Clonal Deletion ◽  
Cell Immunity ◽  
B Cell Immunity

Chronic viral infections subvert protective B cell immunity. An early type I interferon (IFN-I)–driven bias to short-lived plasmablast differentiation leads to clonal deletion, so-called “decimation,” of antiviral memory B cells. Therefore, prophylactic countermeasures against decimation remain an unmet need. We show that vaccination-induced CD4 T cells prevented the decimation of naïve and memory B cells in chronically lymphocytic choriomeningitis virus (LCMV)-infected mice. Although these B cell responses were largely T independent when IFN-I was blocked, preexisting T help assured their sustainability under conditions of IFN-I–driven inflammation by instructing a germinal center B cell transcriptional program. Prevention of decimation depended on T cell–intrinsic Bcl6 and Tfh progeny formation. Antigen presentation by B cells, interactions with antigen-specific T helper cells, and costimulation by CD40 and ICOS were also required. Importantly, B cell–mediated virus control averted Th1-driven immunopathology in LCMV-challenged animals with preexisting CD4 T cell immunity. Our findings show that vaccination-induced Tfh cells represent a cornerstone of effective B cell immunity to chronic virus challenge, pointing the way toward more effective B cell–based vaccination against persistent viral diseases.

scholarly journals B cells in early and chronic HIV infection: evidence for preservation of immune function associated with early initiation of antiretroviral therapy

Blood ◽  
2010 ◽  
Vol 116 (25) ◽  
pp. 5571-5579 ◽  
Author(s):  
Susan Moir ◽  
Clarisa M. Buckner ◽  
Jason Ho ◽  
Wei Wang ◽  
Jenny Chen ◽  
...  
Keyword(s):  
B Cells ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
B Cell ◽  
Immune Cell ◽  
Memory B Cells ◽  
Early Initiation ◽  
Cell Counts ◽  
The Impact ◽  
Chronic Hiv Infection

Abstract Characterization of lymphocytes including B cells during early versus chronic HIV infection is important for understanding the impact of chronic viremia on immune cell function. In this setting, we investigated B cells before and after reduction of HIV plasma viremia by antiretroviral therapy (ART). At baseline, peripheral blood B-cell counts were significantly lower in both early and chronic HIV-infected individuals compared with uninfected controls. Similar to CD4+ but not CD8+ T cells, B-cell numbers in both groups increased significantly after ART. At baseline, B cells of early HIV-infected individuals were composed of a higher percentage of plasmablasts and resting memory B cells compared with chronic HIV-infected individuals whose B cells were composed of a higher percentage of immature/transitional and exhausted B cells compared with their early infection counterparts. At 1 year after ART, the percentage of resting memory B cells remained higher in early compared with chronic HIV-infected individuals. This difference translated into a better functional profile in that memory B-cell responses to HIV and non-HIV antigens were superior in early- compared with chronic-treated HIV infected individuals. These findings provide new insights on B cells in HIV infection and how early initiation of ART may prevent irreversible immune system damage.

scholarly journals Analysis of the heterogeneity of the BCR H-CDR3 repertoire in the bone marrow and spleen of 3-, 12-, and 20-month old mice 

2020 ◽  
Author(s):  
Lina Ma ◽  
Xinsheng Yao ◽  
Tao Xinxin ◽  
He Xiaoyan ◽  
Wang Peng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Mouse Bone Marrow ◽  
Aged Mice ◽  
Cell Immunity ◽  
Repertoire Diversity ◽  
Old Mice ◽  
Peripheral B Cells

Abstract The number of central and peripheral B cells and their responsiveness are decreased in aged mice. The diversity of mouse central and peripheral B cell repertoires with increasing age has not been elucidated. In this study, we demonstrated that there were significant differences in the usage of some V, D, and J genes in the BCR H-CDR3 repertoire of bone marrow B cells, spleen B cells and spleen memory B cells in 3-, 12-, and 20-month-old mice. In the productive, pseudogene, and out-of-frame sequences, bone marrow B cells had significant differences in 5′J trimming with age; peripheral spleen B cells and memory B cells had significant differences in N1 insertion, N2 insertion, P5'D insertion, and 5'D trimming with age. The BCR H-CDR3 repertoire diversity of mouse bone marrow B cells, spleen B cells and spleen memory B cells decreased with increasing age. The proportion of overlap in bone marrow and spleen B cells, but not spleen memory B cells, of mice at different ages was lower at 3 months than at 12 and 20 months. This study is the first to report the homogeneity and heterogeneity of the CDR3 repertoire of central and peripheral B cells change as mice age, to further investigation of the decline and response of B cell immunity in young/middle/old-aged mice.

scholarly journals HIV-Exposed Uninfected Infants Show Robust Memory B-Cell Responses in Spite of a Delayed Accumulation of Memory B Cells: an Observational Study in the First 2 Years of Life

2016 ◽  
Vol 23 (7) ◽  
pp. 576-585 ◽  
Author(s):  
Eunice W. Nduati ◽  
Irene N. Nkumama ◽  
Faith K. Gambo ◽  
Daniel M. Muema ◽  
Miguel G. Knight ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lower Proportion ◽  
Memory B Cells ◽  
Hiv Care ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hiv Exposure ◽  
Hiv Exposed ◽  
The Impact ◽  
Exposed Uninfected

Improved HIV care has led to an increase in the number of HIV-exposed uninfected (HEU) infants born to HIV-infected women. Although they are uninfected, these infants experience increased morbidity and mortality. One explanation may be that their developing immune system is altered by HIV exposure, predisposing them to increased postnatal infections. We explored the impact of HIV exposure on the B-cell compartment by determining the B-cell subset distribution, the frequency of common vaccine antigen-specific memory B cells (MBCs), and the levels of antibodies to the respective antigens in HEU and HIV-unexposed uninfected (HUU) infants born to uninfected mothers, using flow cytometry, a B-cell enzyme-linked immunosorbent spot assay, and an enzyme-linked immunosorbent assay, respectively, during the first 2 years of life. For the majority of the B-cell subsets, there were no differences between HEU and HUU infants. However, HIV exposure was associated with a lower proportion of B cells in general and MBCs in particular, largely due to a lower proportion of unswitched memory B cells. This reduction was maintained even after correcting for age. These phenotypic differences in the MBC compartment did not affect the ability of HEU infants to generate recall responses to previously encountered antigens or reduce the antigen-specific antibody levels at 18 months of life. Although HIV exposure was associated with a transient reduction in the proportion of MBCs, we found that the ability of HEU infants to mount robust MBC and serological responses was unaffected.

scholarly journals Analysis of the heterogeneity of the BCR H-CDR3 repertoire in the bone marrow and spleen of 3-, 12-, and 20-month old mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Lina Ma ◽  
Xinxin Tao ◽  
Xiaoyan He ◽  
Peng Wang ◽  
Long Ma ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Aged Mice ◽  
Cell Immunity ◽  
Different Ages ◽  
Repertoire Diversity ◽  
Old Mice ◽  
Peripheral B Cells

AbstractThe number of central and peripheral B cells and their responsiveness are decreased in aged mice. The diversity of mice central and peripheral B cell repertoires with increasing age has not been elucidated. In this study, we demonstrated that there were significant differences in the usage of some V, D, and J genes in the BCR H-CDR3 repertoire of bone marrow B cells, spleen B cells and spleen memory B cells in 3-, 12-, and 20-month-old mice. In the productive, pseudogene, and out-of-frame sequences, bone marrow B cells had significant differences in 5′J trimming with age; peripheral spleen B cells and memory B cells had significant differences in N1 insertion, N2 insertion, P5’D insertion, and 5’D trimming with age. The BCR H-CDR3 repertoire diversity of mice bone marrow B cells, spleen B cells and spleen memory B cells decreased with increasing age. The proportion of overlap in bone marrow and spleen B cells, but not spleen memory B cells, of mice at different ages was lower at 3 months than at 12 and 20 months. This study is the first to report the homogeneity and heterogeneity of the CDR3 repertoire of central and peripheral B cells change as mice age, to further investigation of the decline and response of B cell immunity in young/middle/old-aged mice.

scholarly journals Memory B Cells in Pregnancy Sensitization

2021 ◽  
Vol 12 ◽  
Author(s):  
Anoma Nellore ◽  
John T. Killian ◽  
Paige M. Porrett
Keyword(s):  
B Cells ◽  
B Cell ◽  
Molecular Mechanisms ◽  
Memory B Cells ◽  
Lymphoid Tissues ◽  
Potential Contribution ◽  
Follicular Helper ◽  
B Cell Subsets ◽  
The Impact ◽  
In Pregnancy

Memory B cells play an important role in immunity to pathogens as these cells are poised to rapidly differentiate into antibody-secreting cells upon antigen re-encounter. Memory B cells also develop over the course of HLA-sensitization during pregnancy and transplantation. In this review, we discuss the potential contribution of memory B cells to pregnancy sensitization as well as the impact of these cells on transplant candidacy and outcomes. We start by summarizing how B cell subsets are altered in pregnancy and discuss what is known about HLA-specific B cell responses given our current understanding of fetal antigen availability in maternal secondary lymphoid tissues. We then review the molecular mechanisms governing the generation and maintenance of memory B cells during infection – including the role of T follicular helper cells - and discuss the experimental evidence for the development of these cells during pregnancy. Finally, we discuss how memory B cells impact access to transplantation and transplant outcomes for a range of transplant recipients.

scholarly journals S protein-reactive IgG and memory B cell production after human SARS-CoV-2 infection includes broad reactivity to the S2 subunit

2020 ◽  
Author(s):  
Phuong Nguyen-Contant ◽  
A. Karim Embong ◽  
Preshetha Kanagaiah ◽  
Francisco A. Chaves ◽  
Hongmei Yang ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Receptor Binding ◽  
Memory B Cells ◽  
Binding Domain ◽  
The Novel ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Cell Immunity ◽  
Antibody Levels

ABSTRACTThe high susceptibility of humans to SARS-CoV-2 infection, the cause of COVID-19, reflects the novelty of the virus and limited preexisting B cell immunity. IgG against the SARS-CoV-2 spike (S) protein, which carries the novel receptor binding domain (RBD), is absent or at low levels in unexposed individuals. To better understand the B cell response to SARS-CoV-2 infection, we asked whether virus-reactive memory B cells (MBCs) were present in unexposed subjects and whether MBC generation accompanied virus-specific IgG production in infected subjects. We analyzed sera and PBMCs from non-SARS-CoV-2-exposed healthy donors and COVID-19 convalescent subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD and S2 subunit, and nucleocapsid [N]) and non-SARS-CoV-2 proteins were related to measurements of circulating IgG MBCs. Anti-RBD IgG was absent in unexposed subjects. Most unexposed subjects had anti-S2 IgG and a minority had anti-N IgG, but IgG MBCs with these specificities were not detected, perhaps reflecting low frequencies. Convalescent subjects had high levels of IgG against the RBD, S2, and N, together with large populations of RBD- and S2-reactive IgG MBCs. Notably, IgG titers against the S protein of the human coronavirus OC43 in convalescent subjects were higher than in unexposed subjects and correlated strongly with anti-S2 titers. Our findings indicate cross-reactive B cell responses against the S2 subunit that might enhance broad coronavirus protection. Importantly, our demonstration of MBC induction by SARS-CoV-2 infection suggests that a durable form of B cell immunity is maintained even if circulating antibody levels wane.IMPORTANCERecent rapid worldwide spread of SARS-CoV-2 has established a pandemic of potentially serious disease in the highly susceptible human population. Key questions are whether humans have preexisting immune memory that provides some protection against SARS-CoV-2 and whether SARS-CoV-2 infection generates lasting immune protection against reinfection. Our analysis focused on pre- and post-infection IgG and IgG memory B cells (MBCs) reactive to SARS-CoV-2 proteins. Most importantly, we demonstrate that infection generates both IgG and IgG MBCs against the novel receptor binding domain and the conserved S2 subunit of the SARS-CoV-2 spike protein. Thus, even if antibody levels wane, long-lived MBCs remain to mediate rapid antibody production. Our study also suggests that SARS-CoV-2 infection strengthens preexisting broad coronavirus protection through S2-reactive antibody and MBC formation.

MO013SENESCENCE-LIKE CHANGES IN B CELL PHENOTYPE IN HEMODIALYSIS PATIENTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Georgios Lioulios ◽  
Asimina Fylaktou ◽  
Aliki Xochelli ◽  
Erasmia Sampani ◽  
Ioannis Tsouchnikas ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Poor Response ◽  
Absolute Number ◽  
Chronic Hemodialysis ◽  
Memory B Cells ◽  
Cell Phenotype ◽  
Cell Immunity ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background and Aims End Stage Renal Disease (ESRD) is characterized by susceptibility to infections, high prevalence of cancer and cardiovascular disease and poor response to vaccination. All of the above are potential consequences to compromised immune function seen in ESRD and demonstrated by profound immune cells phenotype changes, resembling the natural course of senescence; therefore termed immunosenescence. Whereas alterations of T cells in ESRD have been largely studied, there are insufficient data regarding B cell immunity. In this study we evaluate the effects of hemodialysis (HD) on B cells, in terms of untimely expression of immunosenescent phenotype. Method B cells phenotype was analyzed by flow cytometry in 25 ESRD patients on HD (M/F 15/10, Mean Age 59±14.7yrs). Patients on HD with systemic diseases, malignancy or recent (<3 months) episode of infection were excluded. Subpopulations, including naïve (IgD+CD27-), IgM memory (IgD+CD27+), switched memory (IgD-CD27+) and late memory (IgD-CD27-) B cells were determined. Findings were compared to 12 healthy controls of similar age. Results In HD patients a severe B lymphopenia was observed; a decrease in B cells both percentage (6.5±2.7% vs 11.9±4.5%, p<0.0001) and absolute number [88(53) vs 229(271) cells/μl, p<0.0001]. Naïve and late memory B cells proportions were similar between patients and controls, however, absolute number was significantly lower in HD patients for both subsets [55(54)vs118(216) cells/μl, p=0.006, and 7(7) vs 21(24) cells/μl, respectively, p=0.001]. Switched memory B cells declined in HD both in terms of percentage [15.7(11.7)% vs 25.7(18.9)%, p:0.03] and absolute number [13(10) vs 59(64) cells/μl, p=0.00]. Conclusion Chronic hemodialysis results in B cell phenotype alterations similar to normal aging. Switched memory B cells, the predictors of optimal antibody responses are significantly reduced, and this may act as an additional factor to relative immune deficiency of dialysis patients.

scholarly journals S Protein-Reactive IgG and Memory B Cell Production after Human SARS-CoV-2 Infection Includes Broad Reactivity to the S2 Subunit

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Phuong Nguyen-Contant ◽  
A. Karim Embong ◽  
Preshetha Kanagaiah ◽  
Francisco A. Chaves ◽  
Hongmei Yang ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Receptor Binding ◽  
Memory B Cells ◽  
Binding Domain ◽  
The Novel ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Cell Immunity ◽  
Antibody Levels

ABSTRACT The high susceptibility of humans to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the cause of coronavirus disease 2019 (COVID-19), reflects the novelty of the virus and limited preexisting B cell immunity. IgG against the SARS-CoV-2 spike (S) protein, which carries the novel receptor binding domain (RBD), is absent or at low levels in unexposed individuals. To better understand the B cell response to SARS-CoV-2 infection, we asked whether virus-reactive memory B cells (MBCs) were present in unexposed subjects and whether MBC generation accompanied virus-specific IgG production in infected subjects. We analyzed sera and peripheral blood mononuclear cells (PBMCs) from non-SARS-CoV-2-exposed healthy donors and COVID-19 convalescent subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD and S2 subunit, and nucleocapsid [N]) and non-SARS-CoV-2 proteins were related to measurements of circulating IgG MBC levels. Anti-RBD IgG was absent in unexposed subjects. Most unexposed subjects had anti-S2 IgG, and a minority had anti-N IgG, but IgG MBCs with these specificities were not detected, perhaps reflecting low frequencies. Convalescent subjects had high levels of IgG against the RBD, S2, and N, together with large populations of RBD- and S2-reactive IgG MBCs. Notably, IgG titers against the S protein of the human coronavirus OC43 were higher in convalescent subjects than in unexposed subjects and correlated strongly with anti-S2 titers. Our findings indicate cross-reactive B cell responses against the S2 subunit that might enhance broad coronavirus protection. Importantly, our demonstration of MBC induction by SARS-CoV-2 infection suggests that a durable form of B cell immunity is maintained even if circulating antibody levels wane. IMPORTANCE The recent rapid worldwide spread of SARS-CoV-2 has established a pandemic of potentially serious disease in the highly susceptible human population. Key issues are whether humans have preexisting immune memory that provides some protection against SARS-CoV-2 and whether SARS-CoV-2 infection generates lasting immune protection against reinfection. Our analysis focused on pre- and postinfection IgG and IgG memory B cells (MBCs) reactive to SARS-CoV-2 proteins. Most importantly, we demonstrate that infection generates both IgG and IgG MBCs against the novel receptor binding domain and the conserved S2 subunit of the SARS-CoV-2 spike protein. Thus, even if antibody levels wane, long-lived MBCs remain to mediate rapid antibody production. Our study results also suggest that SARS-CoV-2 infection strengthens preexisting broad coronavirus protection through S2-reactive antibody and MBC formation.

scholarly journals Analysis of the heterogeneity of the BCR H-CDR3 repertoire in the bone marrow and spleen of 3-,12-,and20-month old mice

2020 ◽  
Author(s):  
Lina Ma ◽  
Xinsheng Yao
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Mouse Bone Marrow ◽  
Aged Mice ◽  
Cell Immunity ◽  
Different Ages ◽  
Old Mice ◽  
Peripheral B Cells

Abstract The number of central and peripheral B cells and their responsiveness are decreased in agedmice. The diversity of mouse central and peripheral B cell repertoires with increasing age has notbeen elucidated. In this study, we demonstrated that there were significant differences in theusage of some V, D, and J genes in the BCR H-CDR3 repertoire of bone marrow B cells, spleen Bcells and spleen memory B cells in 3-, 12-, and 20-month-old mice. In the productive, pseudogene,and out-of-frame sequences, bone marrow B cells had significant differences in 5′J trimmingwith age; peripheral spleen B cells and memory B cells had significant differences in N1 insertion,N2 insertion, P5'D insertion, and 5'D trimming with age. The BCR H-CDR3 repertoire diversityof mouse bone marrow B cells, spleen B cells and spleen memory B cells decreased withincreasing age. The proportion of overlap in bone marrow and spleen B cells, but not spleenmemory B cells, of mice at different ages was lower at 3 months than at 12 and 20 months.Thisstudy is the first to report the homogeneity and heterogeneity of the CDR3 repertoire of centraland peripheral B cells change as mice age , to further investigation of the decline and response ofB cell immunity in young/middle/old-aged mice.

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