scholarly journals IL-21 and IL-6 Are Critical for Different Aspects of B Cell Immunity and Redundantly Induce Optimal Follicular Helper CD4 T Cell (Tfh) Differentiation

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e17739 ◽  
Author(s):  
Danelle Eto ◽  
Christopher Lao ◽  
Daniel DiToro ◽  
Burton Barnett ◽  
Tania C. Escobar ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cd4 T Cell ◽  
Follicular Helper ◽  
Cell Immunity ◽  
B Cell Immunity

Follicular helper T cell and memory B cell immunity in CHC patients

2019 ◽  
Vol 97 (3) ◽  
pp. 397-407 ◽  
Author(s):  
Yong Liu ◽  
Huifan Ji ◽  
Pingwei Zhao ◽  
Hongqing Yan ◽  
Yanjun Cai ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Helper T Cell ◽  
Memory B Cell ◽  
Follicular Helper ◽  
Cell Immunity ◽  
Follicular Helper T Cell ◽  
B Cell Immunity

scholarly journals Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Adam K. Wheatley ◽  
Jennifer A. Juno ◽  
Jing J. Wang ◽  
Kevin J. Selva ◽  
Arnold Reynaldi ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Vaccine Development ◽  
Natural Infection ◽  
Population Level ◽  
Cell Dynamics ◽  
Follicular Helper ◽  
Cell Immunity ◽  
Specific Igg ◽  
Over Time

AbstractThe durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.

T-cell and B-cell immunity in celiac disease

2015 ◽  
Vol 29 (3) ◽  
pp. 413-423 ◽  
Author(s):  
M. Fleur du Pré ◽  
Ludvig M. Sollid
Keyword(s):  
Celiac Disease ◽  
T Cell ◽  
B Cell ◽  
Cell Immunity ◽  
B Cell Immunity

scholarly journals Human neonatal B cell immunity differs from the adult version by conserved Ig repertoires and rapid, but transient response dynamics

2020 ◽  
Author(s):  
Bettina Budeus ◽  
Artur Kibler ◽  
Martina Brauser ◽  
Ekaterina Homp ◽  
Kevin Bronischewski ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Cord Blood ◽  
B Cell ◽  
Transient Response ◽  
Cell System ◽  
Response Dynamics ◽  
Vaccination Strategies ◽  
Cell Immunity ◽  
B Cell Immunity

AbstractThe human infant B cell system is considered premature or impaired. Here we show that most cord blood B cells are mature and functional as seen in adults, albeit with distinct transcriptional programs providing accelerated responsiveness to T cell-independent and T cell-dependent stimulation and facilitated IgA class switching. Stimulation drives extensive differentiation into antibody-secreting cells, thereby presumably limiting memory B cell formation. The neonatal Ig-repertoire is highly variable, but conserved, showing recurrent B cell receptor (BCR) clonotypes frequently shared between neonates. Our study demonstrates that cord blood B cells are not impaired but differ from their adult counterpart in a conserved BCR repertoire and rapid but transient response dynamics. These properties may account for the sensitivity of neonates to infections and limited effectivity of vaccination strategies. Humanized mice suggest that the distinctness of cord blood versus adult B cells is already reflected by the developmental program of hematopoietic precursors, arguing for a layered B-1/B-2 lineage system as in mice. Still, our findings reveal overall limited comparability of human cord blood B cells and murine B-1 cells.Significance StatementNeonates and infants suffer from enhanced susceptibility to infections. Our study contrasts with the current concept of a premature or impaired B cell system in neonates, by showing that most cord blood B cells are mature and functional. However, their responses are rapid but provide only short-term protection, which may help to improve infant vaccination strategies. We propose an altered perspective on the early human B cell system, which looks similar to but functions differently from the adult counterpart. Finally, our analysis indicates that cord blood- and adult B cell development occur layered as in mice, but certain mouse models still may offer a limited view on human neonatal B cell immunity.

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.

Helper T-cell-regulated B-cell immunity

2003 ◽  
Vol 5 (3) ◽  
pp. 205-212 ◽  
Author(s):  
Michael McHeyzer-Williams ◽  
Louise McHeyzer-Williams ◽  
Joanne Panus ◽  
Rebecca Pogue-Caley ◽  
Gabriel Bikah ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Helper T Cell ◽  
Cell Immunity ◽  
B Cell Immunity

The shifted balance between circulating follicular regulatory T cells and follicular helper T cells in patients with ulcerative colitis

2017 ◽  
Vol 131 (24) ◽  
pp. 2933-2945 ◽  
Author(s):  
Xinrui Wang ◽  
Yonggang Zhu ◽  
Manli Zhang ◽  
Jie Hou ◽  
Hongjuan Wang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
T Cells ◽  
B Cell ◽  
Mayo Clinic ◽  
Treg Cells ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Immune Balance ◽  
Cell Immunity ◽  
B Cell Immunity

B-cell immunity participates in the pathogenesis of ulcerative colitis (UC). The immune balance between follicular regulatory T (TFR) cells and follicular helper T (TFH) cells is important in regulating B-cell responses. However, the alteration of TFR/TFH balance in UC remains unclear. Peripheral blood from 25 UC patients and 15 healthy controls was examined for the frequencies of circulating TFR, TFH, and regulatory T (Treg) cells by flow cytometry. Levels of serum cytokines were measured using cytometric bead array (CBA). Disease activity was evaluated by the Mayo Clinic Score. Compared with controls, UC patients exhibited significant reductions in circulating Foxp3+CXCR5+ TFR cells, the subset interleukin (IL)-10+Foxp3+CXCR5+ cells, and Treg cells, but significant expansions in Foxp3−CXCR5+ TFH cells and IL-21+Foxp3−CXCR5+ cells. UC patients also had reduced levels of serum IL-10 and elevated levels of serum IL-21. The values of Mayo Clinic Score, C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR) in UC patients were negatively correlated with circulating TFR cells, serum IL-10 level, and TFR/TFH ratio, while positively correlated with circulating TFH cells and serum IL-21 level. Alterations in circulating TFR and TFH cells shift the balance from immune tolerance to immune responsive state, contributing to dysregulated B-cell immunity and the pathogenesis of UC.

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 < 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.

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