Dynamics of B-Cell Repertoires and Emergence of Cross-Reactive Responses in COVID-19 Patients with Different Disease Severity

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:10.2139/ssrn.3751051

Cited by 2 publications

(2 citation statements)

References 54 publications

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“…This is in contrast to antibodies with long half-lives, which accumulate over a long period. Although some research groups have reported on the BCR repertoire, to our knowledge, there have been no similar studies focusing on fluctuations in the BCR repertoire over a very short period 15 , 16 , 17 , 18 , 19 .…”

Section: Discussionmentioning

confidence: 99%

Massive surge of mRNA expression of clonal B-cell receptor in patients with COVID-19

Funakoshi

Ohji

Yakushijin

et al. 2021

Heliyon

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Background Antibody production is one of the primary mechanisms for recovery from coronavirus disease 2019 (COVID-19). It is speculated that massive clonal expansion of B cells, which can produce clinically meaningful neutralizing antibodies, occurs in patients who recover on the timing of acquiring adaptive immunity. Methods To evaluate fluctuations in clonal B cells and the size of the clones, we chronologically assessed the B-cell receptor (BCR) repertoire in three patients with COVID-19 who recovered around 10 days after symptom onset. Results We focused on the three dominant clonotypes (top 3) in each individual. The percentage frequencies of the top 3 clonotypes increased rapidly and accounted for 27.8% on day 9 in patient 1, 10.4% on day 12 in patient 2, and 10.8% on day 11 in patient 3, respectively. The frequencies of these top 3 clonotypes rapidly decreased as the patients’ clinical symptoms improved. Furthermore, BCR network analysis revealed that accumulation of clusters composed of similar complementarity-determining region 3 (CDR3) sequences were rapidly formed, grew, and reached their maximum size around 10 days after symptom onset. Conclusions BCR repertoire analysis revealed that a massive surge of some unique BCRs occurs during the acquisition of adaptive immunity and recovery. The peaks were more prominent than expected. These results provide insight into the important role of BCRs in the recovery from COVID-19 and raise the possibility of developing neutralizing antibodies as COVID-19 immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Massive surge of mRNA expression of clonal B-cell receptor in patients with COVID-19

Funakoshi

Ohji

Yakushijin

et al. 2021

Heliyon

View full text Add to dashboard Cite

show abstract

“…Moreover, recent high-throughput sequencing technologies have shown novel perspectives regarding the generation of B cell receptor (BCR) repertoires in a time-and individual-dependent manner, which orchestrate dynamic humoral immune responses against influenza virus, Zika virus (28), Ebola virus (29), and HIV (30). As for SARS-CoV-2, BCR repertoire sequencing revealed the usage frequency of different V and J gene segments and B-cell clonal expansion in infected individuals during the period after symptom onset (31)(32)(33)(34). Nielsen et al reported extensive class switching to IgG and IgA subclasses with limited hypermutations during the initial weeks of COVID-19 infection (31).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Spike Protein Epitopes by Assessing the Dynamics of Humoral Immune Responses in Moderate COVID-19

Chen

Pang

et al. 2022

Front. Immunol.

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The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike protein (S) of SARS-CoV-2 is a major target for diagnosis and vaccine development because of its essential role in viral infection and host immunity. Currently, time-dependent responses of humoral immune system against various S protein epitopes are poorly understood. In this study, enzyme-linked immunosorbent assay (ELISA), peptide microarray, and antibody binding epitope mapping (AbMap) techniques were used to systematically analyze the dynamic changes of humoral immune responses against the S protein in a small cohort of moderate COVID-19 patients who were hospitalized for approximately two months after symptom onset. Recombinant truncated S proteins, target S peptides, and random peptides were used as antigens in the analyses. The assays demonstrated the dynamic IgM- and IgG recognition and reactivity against various S protein epitopes with patient-dependent patterns. Comprehensive analysis of epitope distribution along the spike gene sequence and spatial structure of the homotrimer S protein demonstrated that most IgM- and IgG-reactive peptides were clustered into similar genomic regions and were located at accessible domains. Seven S peptides were generally recognized by IgG antibodies derived from serum samples of all COVID-19 patients. The dynamic immune recognition signals from these seven S peptides were comparable to those of the entire S protein or truncated S1 protein. This suggested that the humoral immune system recognized few conserved S protein epitopes in most COVID-19 patients during the entire duration of humoral immune response after symptom onset. Furthermore, in this cohort, individual patients demonstrated stable immune recognition to certain S protein epitopes throughout their hospitalization period. Therefore, the dynamic characteristics of humoral immune responses to S protein have provided valuable information for accurate diagnosis and immunotherapy of COVID-19 patients.

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Dynamics of B-Cell Repertoires and Emergence of Cross-Reactive Responses in COVID-19 Patients with Different Disease Severity

Cited by 2 publications

References 54 publications

Massive surge of mRNA expression of clonal B-cell receptor in patients with COVID-19

Massive surge of mRNA expression of clonal B-cell receptor in patients with COVID-19

Evaluation of Spike Protein Epitopes by Assessing the Dynamics of Humoral Immune Responses in Moderate COVID-19

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