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Immunol Invest . Landscape of B Cell Receptor Repertoires in COVID-19 Patients Revealed Through CDR3 Sequencing of Immunoglobulin Heavy and Light Ch

tetano

Editor, Senior Moderator
Immunol Invest


. 2022 Jul 7;1-15.
doi: 10.1080/08820139.2022.2092407. Online ahead of print.
Landscape of B Cell Receptor Repertoires in COVID-19 Patients Revealed Through CDR3 Sequencing of Immunoglobulin Heavy and Light Chains


Hongzhi Gao[SUP] 1 2 [/SUP], Liying Yu[SUP] 1 [/SUP], Furong Yan[SUP] 1 [/SUP], Youxian Zheng[SUP] 3 [/SUP], Hongbo Huang[SUP] 4 [/SUP], Xibin Zhuang[SUP] 4 [/SUP], Yiming Zeng[SUP] 2 [/SUP]



Affiliations

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; SARS-CoV-2; heavy chain; light chain.
 
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