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

Yohei Funakoshi,Goh Ohji,Kimikazu Yakushijin,Kei Ebisawa,Yu Arakawa,Jun Saegusa,Hisayuki Matsumoto,Takamitsu Imanishi,Eriko Fukuda,Takaji Matsutani,Yasuko Mori,Kentaro Iwata,Hironobu Minami

doi:10.1016/j.heliyon.2021.e07748

Abstract

BackgroundAntibody 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. MethodsTo 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. ResultsWe 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. ConclusionsBCR 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.

Highlights

Adaptive immunity has been identified as one of the primary mechanisms for protecting humans from infectious diseases [1]
The B-cell receptor (BCR) repertoire assay has been used for immunological research in a variety of fields, including infectious disease, autoimmune disease, and cancer
The frequencies of BCR clonotypes with IGHG1 constant sequence (IgG1) increased after infection relative to IgG2 in all patients (Figure 2D). These results indicate that the alteration in the BCR repertoire immediately after SARS-CoV-2 infection was caused by clonal expansion of several BCR clonotypes

Summary

Introduction

Adaptive immunity has been identified as one of the primary mechanisms for protecting humans from infectious diseases [1]. 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. 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

Objectives

Methods

Results

Conclusion