Dynamics of B cell repertoires and emergence of cross-reactive responses in patients with different severities of COVID-19

Montague, Zachary; Lv, Huibin; Otwinowski, Jakub; DeWitt, William S; Isacchini, Giulio; Yip, Garrick K.; Ng, Wilfred; Tsang, Owen Tak Yin; Yuan, Meng; Liu, Hejun; Wilson, Ian A.; Peiris, J. S. Malik; Wu, Nicholas C.; Nourmohammad, Armita; Mok, Chris Ka Pun

doi:10.1016/j.celrep.2021.109173

Cited by 50 publications

(47 citation statements)

References 77 publications

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“…While asymptomatic COVID-19 patients displayed more abundant TCR diversity, on the contrary, they showed less BCR clonal expansion compared to moderate and severe patients. which is in line with the previous studies 28 , 40 , 41 and are likely to be associated with antibody-secreting B cells that produce antibodies to neutralize the infecting pathogen. 41 , 42 We found that patients with different conditions shared a common IGLV1/2 and IGLJ2/3 usage pattern and IGHV3 and IGHJ4 usage.…”

Section: Discussionsupporting

confidence: 92%

“…which is in line with the previous studies 28 , 40 , 41 and are likely to be associated with antibody-secreting B cells that produce antibodies to neutralize the infecting pathogen. 41 , 42 We found that patients with different conditions shared a common IGLV1/2 and IGLJ2/3 usage pattern and IGHV3 and IGHJ4 usage. Moreover, we found a higher proportion of IGHV3 and IGHJ4 usage in asymptomatic patients.…”

Section: Discussionsupporting

confidence: 92%

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Single-cell immune profiling reveals distinct immune response in asymptomatic COVID-19 patients

Zhao

You

Cui

et al. 2021

Sig Transduct Target Ther

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While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56briCD16− natural killer (NK) cells and upregulation of interferon-gamma in effector CD4+ and CD8+ T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4+ T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Single-cell immune profiling reveals distinct immune response in asymptomatic COVID-19 patients

Zhao

You

Cui

et al. 2021

Sig Transduct Target Ther

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“…Convergent lenient VH-only clonotypes have been identified between multiple SARS-CoV-2 infected or convalescent individuals [ 12 – 18 ] and across different studies, for example the overlap between the clonotypes found by Galson et al . [ 4 ] and Nielsen et al .…”

Section: Introductionmentioning

confidence: 99%

Epitope profiling using computational structural modelling demonstrated on coronavirus-binding antibodies

et al. 2021

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Identifying the epitope of an antibody is a key step in understanding its function and its potential as a therapeutic. Sequence-based clonal clustering can identify antibodies with similar epitope complementarity, however, antibodies from markedly different lineages but with similar structures can engage the same epitope. We describe a novel computational method for epitope profiling based on structural modelling and clustering. Using the method, we demonstrate that sequence dissimilar but functionally similar antibodies can be found across the Coronavirus Antibody Database, with high accuracy (92% of antibodies in multiple-occupancy structural clusters bind to consistent domains). Our approach functionally links antibodies with distinct genetic lineages, species origins, and coronavirus specificities. This indicates greater convergence exists in the immune responses to coronaviruses than is suggested by sequence-based approaches. Our results show that applying structural analytics to large class-specific antibody databases will enable high confidence structure-function relationships to be drawn, yielding new opportunities to identify functional convergence hitherto missed by sequence-only analysis.

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“…However, the usage of the IGHV3-7 gene increased after Hepatitis B vaccination [42]. Also, the abundance of the IGHV4-59, IGHV4-39, IGHV3-23, IGHV3-53, IGH3-66, IGHV2-5, and IGHV2-70 genes was found in SARS-CoV2 infection studies [43][44][45][46]. Similarly, we observed an increased usage of the IGHV3-23 gene on all visits post-vaccination; the usage of the IGHV1-2, IGHV1-18, IGHV3-33, IGHV4-39, IGHV4-31 genes increased at d5, d7 and d10 post-vaccination; and IGHV5-51 was highly used at d10 post-vaccination.…”

Section: Discussionmentioning

confidence: 93%

Longitudinal dynamics of human B-cell response at single-cell level in response to Tdap vaccination

Khatri

Diks

Akker

et al. 2021

Preprint

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Adaptation of the immune system to mount an adequate immune response against pathogens is a crucial function of the adaptive immune system. To better characterize a successful vaccination response, we performed longitudinal (days 0, 5, 7, 10, and 14 after Boostrix vaccination) analysis of the single-cell transcriptome as well as the B-cell receptor (BCR) repertoire (scBCR-rep) in plasma cells of an immunized donor and compared it with baseline B cell characteristics as well as flow cytometry findings. Based on the flow cytometry knowledge and literature findings, we discriminated individual B cell subsets in the transcriptomics data and traced over-time maturation of plasmablasts/plasma cells (PB/PCs) and identified the pathways associated with the plasma cell maturation. We observed that the repertoire in PB/PCs differed from the baseline B cell repertoire e.g. regarding the expansion of unique clones in post-vaccination visits, high usage of IGHG1 in expanded clones, increased class switching events post-vaccination represented by clonotypes spanning multiple IGHC classes and positive selection of CDR3 sequences over time. Importantly, the Variable gene family-based clustering of BCRs represented a similar measure as the gene-based clustering, however, certainly improved the clustering of BCRs, as BCRs from duplicated Variable gene families could be clustered together. Finally, we developed a query tool to dissect the immune response to the components of the Boostrix vaccine. Using this tool, we could identify the BCRs related to anti-tetanus and anti-pertussis toxoids. Collectively, we developed a workflow that allows the description of key features of an ongoing immune response, such as activation of PB/PCs, Ig class switching, somatic hypermutation, and clonal expansion, all of which are hallmarks of antigen exposure.

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Dynamics of B cell repertoires and emergence of cross-reactive responses in patients with different severities of COVID-19

Cited by 50 publications

References 77 publications

Single-cell immune profiling reveals distinct immune response in asymptomatic COVID-19 patients

Single-cell immune profiling reveals distinct immune response in asymptomatic COVID-19 patients

Epitope profiling using computational structural modelling demonstrated on coronavirus-binding antibodies

Longitudinal dynamics of human B-cell response at single-cell level in response to Tdap vaccination

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