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
Affiliations
Yohei Funakoshi
Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine, Kobe, Japan; Corresponding author.
Goh Ohji
Division of Infection Disease Therapeutics, Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Clinical Laboratory, Kobe University Hospital, Kobe, Japan
Kimikazu Yakushijin
Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine, Kobe, Japan
Kei Ebisawa
Division of Infection Disease Therapeutics, Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan
Yu Arakawa
Division of Infection Disease Therapeutics, Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan
Jun Saegusa
Department of Clinical Laboratory, Kobe University Hospital, Kobe, Japan
Hisayuki Matsumoto
Department of Clinical Laboratory, Kobe University Hospital, Kobe, Japan
Takamitsu Imanishi
Department of Clinical Laboratory, Kobe University Hospital, Kobe, Japan
Eriko Fukuda
National Institute of Advanced Industrial Science and Technology, Cellular and Molecular Biotechnology Research Institute, Tokyo, Japan
Takaji Matsutani
Research & Development Department, Repertoire Genesis Inc., Ibaraki, Japan
Yasuko Mori
Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan
Kentaro Iwata
Division of Infection Disease Therapeutics, Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan
Hironobu Minami
Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine, Kobe, Japan; Cancer Center, Kobe University Hospital, Kobe, Japan
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.
