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 TP53INP1 deficiency maintains murine B lymphopoiesis in aged bone marrow through redox-controlled IL-7R/STAT5 signaling

2018 ◽  
Vol 116 (1) ◽  
pp. 211-216 ◽  
Author(s):  
Bochra Zidi ◽  
Christelle Vincent-Fabert ◽  
Laurent Pouyet ◽  
Marion Seillier ◽  
Amelle Vandevelde ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Immune Cell ◽  
B Lymphopoiesis ◽  
Hematopoietic Stem ◽  
Chronic Oxidative Stress ◽  
The Impact ◽  
Deficient Mice

Bone marrow (BM) produces all blood and immune cells deriving from hematopoietic stem cells (HSCs). The decrease of immune cell production during aging is one of the features of immunosenescence. The impact of redox dysregulation in BM aging is still poorly understood. Here we use TP53INP1-deficient (KO) mice endowed with chronic oxidative stress to assess the influence of aging-associated redox alterations in BM homeostasis. We show that TP53INP1 deletion has no impact on aging-related accumulation of HSCs. In contrast, the aging-related contraction of the lymphoid compartment is mitigated in TP53INP1 KO mice. B cells that accumulate in old KO BM are differentiating cells that can mature into functional B cells. Importantly, this phenotype results from B cell-intrinsic events associated with defective redox control. Finally, we show that oxidative stress in aged TP53INP1-deficient mice maintains STAT5 expression and activation in early B cells, driving high Pax5 expression, which provides a molecular mechanism for maintenance of B cell development upon aging.

Long Term Humoral Immune Reconstitution Kinetics After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) In Children

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4627-4627
Author(s):  
Amro Elshoury ◽  
Neena Kapoor ◽  
Ami J Shah ◽  
Bhakti Mehta ◽  
Kris M. Mahadeo ◽  
...  
Keyword(s):  
B Cells ◽  
Serum Level ◽  
B Cell ◽  
Immune Reconstitution ◽  
Serum Levels ◽  
Multivariate Regression Analysis ◽  
Memory B Cells ◽  
Post Transplantation ◽  
Humoral Immune ◽  
Cell Counts

Background HSCT recipients have increased incidence of acquiring infections, particularly by encapsulated bacteria such as Streptococcal pneumoniae and Haemophilus influenzae. Delayed immune reconstitution has a pivotal role in these complications. Although T-cell immune reconstitution has been well studied, long-term B-cell reconstitution remains less characterized. Patients and Methods We studied 73 patients, who received allogeneic HSCT at Childrens Hospital Los Angeles. Patients were in complete remission of their underlying disorder and with median follow up 4.15 years [yrs] (range 6 month -18yrs, mean 5 yrs) post-HSCT. All subjects were< 18 years of age. B (naive [IgD+CD27-CD19+], memory [IgD+CD27+CD19+] and switched memory [IgD-CD27+CD19]); and T (CD3+, CD3+CD4+, CD3+CD8+, CD4+CD25+CD127dim (T Regulatory) [Tregs], RA+CD4+) cell subtypes, quantitative Immunoglobulins levels and antibodies to both polyribosyle polyphospate (PRP) and tetanus toxoid (TT) antigens were assessed longitudinally after HSCT. Results Naive B Cells were the first B cell subtype to return to normal value at 6 month post-HSCT, while memory B cells were persistently low up to two years post-HSCT. PRP levels continued to be low up to 10 years post -HSCT in unrelated donor HSCT recipients. TT antibodies level was normal at 6 month post-HSCT following immunization with TT in patients not receiving IVIG therapy. Switched memory B cell counts correlated positively with RA+CD4+ counts at 6 month post-HSCT (r=0.459, P=0.021) and with CD3+CD+4 counts at 6 months (r=0.530, P=0.006) and 2-years post-HSCT (r=0.398, P=0.016). However, switched memory B cells did not correlate with Tregs at any time post-HSCT. Switched memory B cells correlated positively with serum level of IgG at 1 (r=0.443, P=0.039), and 2 years post transplantation (r=0.617, P=0.001) and with serum level of IgA at 2 years post-HSCT(r=0.567. P=0.004). Memory B-cells counts correlated positively with serum levels of IgM at 1 year post-HSCT (r=0.478, P=0.021) and with serum levels of both IgG and IgA (r=0.431 P=0.035, and r=0.416, P=0.043, respectively) at 2 years post-HSCT. However, memory B-cell counts did not correlate with RA+CD4+, CD3+CD4+, CD3+CD8+ or Tregs cell counts. The use of Total body irradiation (TBI) was associated with lower switched memory B cells at 2 years (P=0.01) post-HSCT. TBI recipients also have lower PRP levels at 6-month post-HSCT compared to patients who did not receive TBI. Age of the recipient at time transplantation is another independent factor affecting all the B cell subsets recovery after transplantation; increase in age at transplantation is associated with lower B cell recovery. Decreased memory B cells post-HSCT was observed in patients with history of acute graft versus host disease (GVHD) (P=0.034) and chronic GVHD (P=0.01), even after resolution of clinical manifestations of active GVHD at 6 month and 2 years follow up, respectively. Compared to cord blood graft recipients, Bone marrow graft recipients have increased switched memory B-cells at 6 month and higher (P=0.0001) PRP antibodies titer at 3 years post-HSCT, respectively. Patients who did not receive ATG or Alemtuzumab have increased recovery of naive B-cells (P=0.024) at 2 years post-transplantation. Patients received ATG have higher both naive B cells in univariate analysis and PRP levels (in multivariate analysis) than those received Alemtuzumab at 6 months post-HSCT. Multivariate regression analysis showed that patients received Alemtuzumab have higher TT antibodies titer at 6 month post -HSCT compared to those received ATG. Conclusion We have found that memory and switched memory B-cells and serum PRP levels are deficient post-HSCT in children. Switched memory B cells correlated positively with serum level of IgG and IgA and memory B-cells correlated positively with serum levels of IgM, IgG and IgA. This confirms that HSCT recipients have impaired humoral immune reconstitution, hindering both B-cells development and generation of immunoglobulins. We also studied the different factors affecting humoral immune reconstitution using backwards multivariate regression analysis model and found that the use of TBI, age of the recipient at transplantation, GVHD status and source of stem cells can affect the kinetics of humoral immune reconstitution after HSCT in children. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Roles of activating functions 1 and 2 of estrogen receptor α in lymphopoiesis

2018 ◽  
Vol 236 (2) ◽  
pp. 99-109 ◽  
Author(s):  
Annica Andersson ◽  
Anna E Törnqvist ◽  
Sofia Moverare-Skrtic ◽  
Angelina I Bernardi ◽  
Helen H Farman ◽  
...  
Keyword(s):  
Immune System ◽  
B Cells ◽  
Estrogen Receptors ◽  
B Cell ◽  
Sex Steroids ◽  
Cellular Response ◽  
Immune Cell ◽  
Cell Development ◽  
B Lymphopoiesis ◽  
The Impact

Apart from the role of sex steroids in reproduction, sex steroids are also important regulators of the immune system. 17β-estradiol (E2) represses T and B cell development, but augments B cell function, possibly explaining the different nature of immune responses in men and women. Both E2 and selective estrogen receptors modulators (SERM) act via estrogen receptors (ER). Activating functions (AF)-1 and 2 of the ER bind to coregulators and thus influence target gene transcription and subsequent cellular response to ER activation. The importance of ERαAF-1 and AF-2 in the immunomodulatory effects of E2/SERM has previously not been reported. Thus, detailed studies of T and B lymphopoiesis were performed in ovariectomized E2-, lasofoxifene- or raloxifene-treated mice lacking either AF-1 or AF-2 domains of ERα, and their wild-type littermate controls. Immune cell phenotypes were analyzed with flow cytometry. All E2 and SERM-mediated inhibitory effects on thymus cellularity and thymic T cell development were clearly dependent on both ERαAFs. Interestingly, divergent roles of ERαAF-1 and ERαAF-2 in E2 and SERM-mediated modulation of bone marrow B lymphopoiesis were found. In contrast to E2, effects of lasofoxifene on early B cells did not require functional ERαAF-2, while ERαAF-1 was indispensable. Raloxifene reduced early B cells partly independent of both ERαAF-1 and ERαAF-2. Results from this study increase the understanding of the impact of ER modulation on the immune system, which can be useful in the clarification of the molecular actions of SERMs and in the development of new SERM.

scholarly journals Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Chun-Shu Wong ◽  
Clarisa M. Buckner ◽  
Silvia Lucena Lage ◽  
Luxin Pei ◽  
Felipe L. Assis ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Antiretroviral Therapy ◽  
B Cell ◽  
Germinal Center ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Cd4 T Cell ◽  
Follicular Helper ◽  
Cell Counts

Low nadir CD4 T-cell counts in HIV+ patients are associated with high morbidity and mortality and lasting immune dysfunction, even after antiretroviral therapy (ART). The early events of immune recovery of T cells and B cells in severely lymphopenic HIV+ patients have not been fully characterized. In a cohort of lymphopenic (CD4 T-cell count &lt; 100/µL) HIV+ patients, we studied mononuclear cells isolated from peripheral blood (PB) and lymph nodes (LN) pre-ART (n = 40) and 6-8 weeks post-ART (n = 30) with evaluation of cellular immunophenotypes; histology on LN sections; functionality of circulating T follicular helper (cTfh) cells; transcriptional and B-cell receptor profile on unfractionated LN and PB samples; and plasma biomarker measurements. A group of 19 healthy controls (HC, n = 19) was used as a comparator. T-cell and B-cell lymphopenia was present in PB pre-ART in HIV+ patients. CD4:CD8 and CD4 T- and B-cell PB subsets partly normalized compared to HC post-ART as viral load decreased. Strikingly in LN, ART led to a rapid decrease in interferon signaling pathways and an increase in Tfh, germinal center and IgD-CD27- B cells, consistent with histological findings of post-ART follicular hyperplasia. However, there was evidence of cTfh cells with decreased helper capacity and of limited B-cell receptor diversification post-ART. In conclusion, we found early signs of immune reconstitution, evidenced by a surge in LN germinal center cells, albeit limited in functionality, in HIV+ patients who initiate ART late in disease.

scholarly journals Loss of memory B cells during chronic HIV infection is driven by Foxo3a- and TRAIL-mediated apoptosis

2012 ◽  
Vol 122 (7) ◽  
pp. 2704-2704
Author(s):  
Julien van Grevenynghe ◽  
Rafael A. Cubas ◽  
Alessandra Noto ◽  
Sandrina DaFonseca ◽  
Zhong He ◽  
...  
Keyword(s):  
B Cells ◽  
Hiv Infection ◽  
Memory B Cells ◽  
Chronic Hiv Infection

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 OP0136 RITUXIMAB PREVENTS THE PROGRESSION OF B-CELL DRIVEN INFLAMMATORY INFILTRATE IN THE MINOR SALIVARY GLANDS OF PRIMARY SJOGREN’S SYNDROME BY DOWNREGULATING IMMUNOLOGICAL PATHWAYS KEY IN ECTOPIC GERMINAL CENTRE ORGANIZATION: RESULTS FROM THE TRACTISS TRIAL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 79-80
Author(s):  
E. Pontarini ◽  
F. Chowdhury ◽  
E. Sciacca ◽  
S. Grigoriadou ◽  
F. Rivellese ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Histological Analysis ◽  
Immune Cell ◽  
Salivary Flow ◽  
Memory B Cells ◽  
Cell Recruitment ◽  
Immune Cell Recruitment

Background:The pathogenic role of B-cells in primary Sjögren’s Syndrome (pSS) is well established and B cell abnormalities. Because of the substantial role of B-cells, rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, has been considered as a potential biologic disease modifying drug to reduce disease activity in pSS. To date, the TRial for Anti-B-Cell Therapy In patients with pSS (TRACTISS) is the largest multi-centre, placebo-controlled trial with RTX. Despite the unmet primary endpoints (30% reduction in fatigue or oral dryness, measured by visual analogue scale), RTX treated patients showed an improvement in unstimulated whole salivary flow (Bowman et al. Arthritis Rheumatol 2017;69:1440–1450).Objectives:To provide the first longitudinal transcriptomic and histological analysis at 3 time points over 48 weeks of labial SGs of pSS patients treated with RTX, in comparison to placebo, from the TRACTISS cohort.Methods:26 pSS patients randomised to RTX or placebo arm consented for labial SG biopsies at baseline, weeks 16 and 48. Patients received two 1000mg cycles of RTX or placebo at baseline and week 24. SG focus score, inflammatory aggregate area fraction, B-cells (CD20+), T-cells (CD3+), follicular dendritic cells (FDCs) (CD21+) and plasma cells (CD138+) density were assessed by H&E and immunofluorescence staining. The histological analysis was performed by digital imaging using QuPath software. RNA was extracted from matched labial SG lobules and sequenced with Illumina platform. A Principal Component Analysis (PCA) and features driving the PCA were investigated along with the most influential gene loadings. The limma-voom R pipeline was used to extract Differential Expressed Genes (DEGs) between placebo and RTX group at week 48, and gene ontology (GO) enrichment analysis performed through EnrichR to derive GO terms and pathways associated with DEGs.Results:Placebo-treated labial SGs showed a worsening of inflammation highlighted by the increment of B-cell density, development of new FDC networks, and a higher ectopic GC prevalence at week 48, compared to RTX-treated patients. No difference in total T-cells and plasma cell infiltration was observed. RTX downregulated genes involved in immune cell recruitment and inflammatory aggregate organisation (e.g. CCR7, CCL19, CD52, and PDCD1) and gene signature-based analysis of 64 immune cell types highlighted how RTX preferentially blocked class-switched- and memory-B-cells infiltration in SGs at week 48. Pathway analyses confirmed the downregulation of leukocyte migration, MHC class II antigen presentation, and T-cell co-stimulation immunological pathways, such as the CD40 receptor complex pathway. The analysis of placebo SGs transcriptomic at week 48 showed a higher expression of genes linked to ectopic GC organisation, such as CXCL13, CCL19, LTβ, in female compared to male subjects. Gender was confirmed as a key co-variate responsible for most of the variation in the PCA, together with the SG focus score and the foci area fraction.Conclusion:Treatment with RTX showed beneficial effects on labial SG inflammatory infiltration in pSS, by downregulating genes involved in immune cell recruitment, activation and organisation in ectopic GCs. Class-switched-B-cells, memory-B-cells and FDC network development were primarily affected appearing to be responsible for the lack of progression in SG B cell infiltration in the RTX compared to the placebo arm in which clear worsening of SG immunopathology over 48 weeks was detected in female patients. Although a clear association with the clinical improvement in unstimulated salivary flow observed at week 48 in RTX-treated patients could not be established given the low number of patients consenting to 3 longitudinal biopsies it is conceivable that RTX is responsible for preserving exocrine function.Acknowledgements:SJB receives a salary contribution from the NIHR Birmingham Biomedical Research Centre.Disclosure of Interests:Elena Pontarini: None declared, Farzana Chowdhury: None declared, Elisabetta Sciacca: None declared, Sofia Grigoriadou: None declared, Felice Rivellese: None declared, Davide Lucchesi: None declared, Katriona Goldmann: None declared, Liliane Fossati-Jimack: None declared, Paul Emery: None declared, Wan Fai Ng: None declared, Nurhan Sutcliffe: None declared, Colin Everett: None declared, Catherine Fernandez: None declared, Anwar Tappuni: None declared, Myles Lewis: None declared, Costantino Pitzalis: None declared, Simon J. Bowman Consultant of: SJB In 2020 I have received consultancy fees from Novartis, Abbvie and Galapagos., Michele Bombardieri: None declared

scholarly journals Alteration in Oral Microbiome Among Men Who Have Sex With Men With Acute and Chronic HIV Infection on Antiretroviral Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Shuang Li ◽  
Junping Zhu ◽  
Bin Su ◽  
Huanhuan Wei ◽  
Fei Chen ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Hiv Infections ◽  
Oral Microbiome ◽  
People Living With Hiv ◽  
Acute Hiv Infection ◽  
Cell Counts ◽  
Acute Hiv ◽  
Sex With Men ◽  
Chronic Hiv Infection

Despite the antiretroviral therapy (ART), human immunodeficiency virus (HIV)-related oral disease remains a common problem for people living with HIV (PLWH). Evidence suggests that impairment of immune function in HIV infection might lead to the conversion of commensal bacteria to microorganisms with increased pathogenicity. However, limited information is available about alteration in oral microbiome in PLWH on ART. We performed a longitudinal comparative study on men who have sex with men (MSM) with acute HIV infection (n=15), MSM with chronic HIV infection (n=15), and HIV-uninfected MSM controls (n=15). Throat swabs were collected when these subjects were recruited (W0) and 12 weeks after ART treatment (W12) from the patients. Genomic DNAs were extracted and 16S rRNA gene sequencing was performed. Microbiome diversity was significantly decreased in patients with acute and chronic HIV infections compared with those in controls at the sampling time of W0 and the significant difference remained at W12. An increased abundance of unidentified Prevotellaceae was found in patients with acute and chronic HIV infections. Moreover, increased abundances of Prevotella in subjects with acute HIV infection and Streptococcus in subjects with chronic HIV infection were observed. In contrast, greater abundance in Lactobacillus, Rothia, Lautropia, and Bacteroides was found in controls. After effective ART, Bradyrhizobium was enriched in both acute and chronic HIV infections, whereas in controls, Lactobacillus, Rothia, Clostridia, Actinobacteria, and Ruminococcaceae were enriched. In addition, we found that lower CD4+ T-cell counts (&lt;200 cells/mm3) were associated with lower relative abundances of Haemophilus, Actinomyces, unidentified Ruminococcaceae, and Rothia. This study has shown alteration in oral microbiome resulting from HIV infection and ART. The results obtained warrant further studies in a large number of subjects with different ethnics. It might contribute to improved oral health in HIV-infected individuals.

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.

Sign in / Sign up

Export Citation Format

Share Document