Landscape of B Cell Receptor Repertoires in COVID-19 Patients Revealed Through CDR3 Sequencing of Immunoglobulin Heavy and Light Chains

ABSTRACT

The outbreak and persistence of coronavirus disease 2019 (COVID-19) threaten human health. B cells play a vital role in fighting the infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite many studies on the immune responses in COVID-19 patients, it is still unclear how B cell receptor (BCR) constituents, including immunoglobulin heavy (IGHs) and light chains (IGLs), respond to SARS-CoV-2 in patients with varying symptoms. In this study, we conducted complementarity-determining region 3 (CDR3) sequencing of BCR IGHs and IGLs from the peripheral blood of COVID-19 patients and healthy donors. The results showed significantly reduced clonal diversity, more expanded clones, and longer CDR3 lengths of IGH and IGL in COVID-19 patients than those in healthy individuals. The IGLs had a much higher percentage of VJ skew usage (47.83% IGLV and 42.86% IGLJ were significantly regulated) than the IGHs (12.09% IGHV and 0% IGHJ) between the healthy individuals and patients, which indicated the importance of BCR light chains. Furthermore, we found a largely expanded IGLV3-25 gene cluster mostly pairing with IGLJ1 and ILGJ2 in COVID-19 patients and a newly identified upregulated IGLJ1 gene and IGLJ2+IGLV13-21 recombination, both of which are potential sources of SARS-CoV-2-targeting antibodies. Our findings on specific immune B-cell signatures associated with COVID-19 have clinical implications for vaccine and biomarker development for disease diagnosis.

KEYWORDS:

• BCR sequencing
• COVID-19
• heavy chain
• light chain
• SARS-CoV-2

Acknowledgments

We wish to thank Yichuang Lin for his assistance in sample information collection.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics statement

The blood samples were provided by the Second Affiliated Hospital of Fujian Medical University (Quanzhou, Fujian, China) with the approval of the institutional research board and the donors’ consent. Procedures followed in this study were under the ethical standards of concerned institutional policies.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/08820139.2022.2092407.

Additional information

Funding

This work was supported by the Emergency Public Project of Fujian Medical University under Grant [number 2020YJ008].