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

Abstract

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.

Convergent CDR3 homology amongst Spike-specific antibody responses in convalescent COVID-19 subjects receiving the BNT162b2 vaccine

“…Matching B cell heavy chain V and J genes and assessing sequence similarity in the heavy chain CDR3 (CDRH3) region are criteria typically used to identify similar B cell clonotypes in different subject cohorts [ 19 , 21 , 22 , 32 , [34] , [35] , [36] , [37] , [38] ]. Clonotypes from both naïve BNT162b2 vaccinees [ 21 , 22 , 32 ] and convalescent unvaccinated individuals [ 19 , [34] , [35] , [36] , [37] , [38] ] have been found to be homologous with published antibodies and/or amongst different individuals based on the above criteria, showing convergent development of conserved variable region genes and sequences that work to target SARS-CoV-2. Many of these clonotypes have been identified to specifically target RBD, with subsets of these antibody clones shown to be neutralizing [ 32 , 34 , 36 ].…”

Response to mRNA SARS‐CoV‐2 vaccination evaluated by B‐cell receptor repertoire after tixagevimab/cilgavimab administration

“…We previously reported a massive surge in mRNA expression of several BCR chronotypes in COVID-19 patients 2 weeks after disease onset and decreased within 1 week. 22 Therefore, we have believed that in order to measure the whole activity of humoral immunity using BCR repertoire assay, it is important that analysis should be done soon after SARS-CoV-2 infection. 22 However, regarding SARS-CoV-2-specific sequences, the frequency was only 0.1%-2% around 2 weeks after onset (Figure 2B).…”

“…22 Therefore, we have believed that in order to measure the whole activity of humoral immunity using BCR repertoire assay, it is important that analysis should be done soon after SARS-CoV-2 infection. 22 However, regarding SARS-CoV-2-specific sequences, the frequency was only 0.1%-2% around 2 weeks after onset (Figure 2B). We speculate that it is difficult to determine the specific immune response against SARS-CoV-2 from the total BCR repertoire data.…”

Identifying hub genes and common biological pathways between COVID-19 and benign prostatic hyperplasia by machine learning algorithms

“…According to KEGG data, these genes seem to be abundant in pathways related to inflammation and infection, including the B-cell receptor signaling pathway, inflammatory bowel disease, and cytotoxicity mediated by natural killer cells. The role of B cells in immunity to SARS-CoV-2 infection and vaccination has been demonstrated in several studies, and the type of SARS-CoV-2 exposure has distinct effects on the formation of B cell receptors (47)(48)(49)(50). Russell et al thought that the spleens of COVID-19 patients had higher levels of some components of the B cell signaling pathway (51).…”